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Gene Information
Gene symbol: TNFRSF10A
Gene name: tumor necrosis factor receptor superfamily, member 10a
HGNC ID: 11904
Synonyms: DR4, Apo2, TRAILR-1, CD261
Related Genes
| # | Gene Symbol | Number of hits |
| 1 | BAK1 | 1 hits |
| 2 | BAX | 1 hits |
| 3 | BBC3 | 1 hits |
| 4 | BCL2 | 1 hits |
| 5 | BCL2L1 | 1 hits |
| 6 | BCL2L11 | 1 hits |
| 7 | BRWD2 | 1 hits |
| 8 | C21orf63 | 1 hits |
| 9 | C4A | 1 hits |
| 10 | C4B | 1 hits |
| 11 | CASP3 | 1 hits |
| 12 | CD4 | 1 hits |
| 13 | CD8A | 1 hits |
| 14 | COL9A3 | 1 hits |
| 15 | CTLA4 | 1 hits |
| 16 | DGCR2 | 1 hits |
| 17 | DR1 | 1 hits |
| 18 | DYNLT1 | 1 hits |
| 19 | GAD1 | 1 hits |
| 20 | GAD2 | 1 hits |
| 21 | GLO1 | 1 hits |
| 22 | HAGH | 1 hits |
| 23 | HLA-A | 1 hits |
| 24 | HLA-B | 1 hits |
| 25 | HLA-DOB | 1 hits |
| 26 | HLA-DQA1 | 1 hits |
| 27 | HLA-DRB1 | 1 hits |
| 28 | HNF1A | 1 hits |
| 29 | IDDM2 | 1 hits |
| 30 | IGKV1-17 | 1 hits |
| 31 | IGKV2-23 | 1 hits |
| 32 | INS | 1 hits |
| 33 | KIR2DL1 | 1 hits |
| 34 | KIR2DL2 | 1 hits |
| 35 | LTA | 1 hits |
| 36 | MCL1 | 1 hits |
| 37 | MICA | 1 hits |
| 38 | MRAP | 1 hits |
| 39 | MT3 | 1 hits |
| 40 | NDUFA5 | 1 hits |
| 41 | NDUFB4 | 1 hits |
| 42 | PMAIP1 | 1 hits |
| 43 | PPY | 1 hits |
| 44 | PTPN22 | 1 hits |
| 45 | PTPRN | 1 hits |
| 46 | RANGAP1 | 1 hits |
| 47 | SEC14L2 | 1 hits |
| 48 | SUMO4 | 1 hits |
| 49 | TAP2 | 1 hits |
| 50 | TNF | 1 hits |
| 51 | TNFRSF10B | 1 hits |
| 52 | TNFRSF10C | 1 hits |
| 53 | TNFRSF10D | 1 hits |
| 54 | TNFRSF21 | 1 hits |
| 55 | TNFRSF25 | 1 hits |
| 56 | TNFSF10 | 1 hits |
| 57 | TOR1A | 1 hits |
| 58 | TP53 | 1 hits |
| 59 | WFS1 | 1 hits |
Related Sentences
| # | PMID | Sentence |
| 1 | 1348711 | In Finland the haplotype-specific absolute risk for developing Type 1 diabetes differs between various DR3 and DR4 positive haplotypes. |
| 2 | 1348711 | The absolute risk for Type 1 diabetes for DR4,DQw8 positive haplotypes A2,Cw4,Bw35,DR4 A3,Cw3,Bw62,DR4, A24,Cw7,Bw39,DR4, A2,Cw3,Bw62, DR4, and A2,Cw1,Bw56,DR4 was 35/100,000, 130/100,000, 166/100,000, 196/100,000, and 218/100,000, respectively. |
| 3 | 1348711 | In Finland the haplotype-specific absolute risk for developing Type 1 diabetes differs between various DR3 and DR4 positive haplotypes. |
| 4 | 1348711 | The absolute risk for Type 1 diabetes for DR4,DQw8 positive haplotypes A2,Cw4,Bw35,DR4 A3,Cw3,Bw62,DR4, A24,Cw7,Bw39,DR4, A2,Cw3,Bw62, DR4, and A2,Cw1,Bw56,DR4 was 35/100,000, 130/100,000, 166/100,000, 196/100,000, and 218/100,000, respectively. |
| 5 | 1349195 | The DR9-associated disease-susceptibility allele in Japanese subjects is distinct from both the DR3- and DR4-associated susceptibility alleles in white Caucasians. |
| 6 | 1355747 | By using the aetiologic fraction (delta) as an almost absolute measure of the strongest linkage disequilibrium of an HLA marker to the putative Type 1 diabetes susceptibility locus, it has been found that the strength of association of the HLA markers may be quantified as follows: DR4 less than DR3 less than DR3 or DR4 less than non-Aspartate 57 beta DQ and Arginine 52 alpha DQ less than Arginine 52 alpha DQ. |
| 7 | 1355747 | Thus, molecular HLA-DQ markers appear to be more accurate as susceptibility markers than the classic serologically defined ones (DR3 and DR4); however, any effect of DQ markers disappears when non-DR3/DR4 individuals are considered, suggesting that DR factors (or others in between DQ and DR) are also important. |
| 8 | 1355747 | By using the aetiologic fraction (delta) as an almost absolute measure of the strongest linkage disequilibrium of an HLA marker to the putative Type 1 diabetes susceptibility locus, it has been found that the strength of association of the HLA markers may be quantified as follows: DR4 less than DR3 less than DR3 or DR4 less than non-Aspartate 57 beta DQ and Arginine 52 alpha DQ less than Arginine 52 alpha DQ. |
| 9 | 1355747 | Thus, molecular HLA-DQ markers appear to be more accurate as susceptibility markers than the classic serologically defined ones (DR3 and DR4); however, any effect of DQ markers disappears when non-DR3/DR4 individuals are considered, suggesting that DR factors (or others in between DQ and DR) are also important. |
| 10 | 1357169 | Accordingly, no overrepresentation of homozygosity for HLA-DR4 was found among the total number of 25 patients with RA as well as insulin dependent diabetes mellitus, though the opposite might be expected as these diseases have a common DR4 association--RA with DR4 and DR1 and insulin dependent diabetes mellitus with DR4 and DR3. |
| 11 | 1360432 | Among Australians heterozygous for HLA-DR3, DR4, 85% were positive for antibodies to glutamic acid decarboxylase, significantly different (p = 0.039) from the prevalence of 48% in patients with at least one HLA-DR antigen other than DR3 or DR4. |
| 12 | 1361076 | The genes located between class II and class I HLA genes including polymorphic tumour necrosis factor (TNF) genes may contribute to the disease susceptibility in IDDM. |
| 13 | 1361076 | Restriction fragment polymorphisms of the TNF-beta gene have been found to be fixed in the major IDDM susceptibility haplotypes, the B62,DR4 haplotype being associated with the 10.5-kb fragment and the B8,DR3 haplotype with a 5.5-kb fragment. |
| 14 | 1361076 | Among IDDM haplotypes the B62,DR4 haplotype was characterized by the 10.5-kb TNF fragment, whereas two other common Finnish IDDM-associated DR4 haplotypes--A24,B39,DR4 and A2,B56,DR4--had the 5.5-kb TNF fragment. |
| 15 | 1361076 | Both IDDM-associated and non-associated DR3 positive haplotypes were linked to the 5.5-kb fragment. |
| 16 | 1361076 | The distribution of various combinations of TNF alleles in IDDM probands (n = 63) did not differ from that expected according to the Hardy-Weinberg distribution. |
| 17 | 1361076 | Our results indicate that the 10.5-kb allele of TNF-beta gene as such is not a risk factor contributing to DR4/DQ8-associated susceptibility. |
| 18 | 1361076 | The genes located between class II and class I HLA genes including polymorphic tumour necrosis factor (TNF) genes may contribute to the disease susceptibility in IDDM. |
| 19 | 1361076 | Restriction fragment polymorphisms of the TNF-beta gene have been found to be fixed in the major IDDM susceptibility haplotypes, the B62,DR4 haplotype being associated with the 10.5-kb fragment and the B8,DR3 haplotype with a 5.5-kb fragment. |
| 20 | 1361076 | Among IDDM haplotypes the B62,DR4 haplotype was characterized by the 10.5-kb TNF fragment, whereas two other common Finnish IDDM-associated DR4 haplotypes--A24,B39,DR4 and A2,B56,DR4--had the 5.5-kb TNF fragment. |
| 21 | 1361076 | Both IDDM-associated and non-associated DR3 positive haplotypes were linked to the 5.5-kb fragment. |
| 22 | 1361076 | The distribution of various combinations of TNF alleles in IDDM probands (n = 63) did not differ from that expected according to the Hardy-Weinberg distribution. |
| 23 | 1361076 | Our results indicate that the 10.5-kb allele of TNF-beta gene as such is not a risk factor contributing to DR4/DQ8-associated susceptibility. |
| 24 | 1361076 | The genes located between class II and class I HLA genes including polymorphic tumour necrosis factor (TNF) genes may contribute to the disease susceptibility in IDDM. |
| 25 | 1361076 | Restriction fragment polymorphisms of the TNF-beta gene have been found to be fixed in the major IDDM susceptibility haplotypes, the B62,DR4 haplotype being associated with the 10.5-kb fragment and the B8,DR3 haplotype with a 5.5-kb fragment. |
| 26 | 1361076 | Among IDDM haplotypes the B62,DR4 haplotype was characterized by the 10.5-kb TNF fragment, whereas two other common Finnish IDDM-associated DR4 haplotypes--A24,B39,DR4 and A2,B56,DR4--had the 5.5-kb TNF fragment. |
| 27 | 1361076 | Both IDDM-associated and non-associated DR3 positive haplotypes were linked to the 5.5-kb fragment. |
| 28 | 1361076 | The distribution of various combinations of TNF alleles in IDDM probands (n = 63) did not differ from that expected according to the Hardy-Weinberg distribution. |
| 29 | 1361076 | Our results indicate that the 10.5-kb allele of TNF-beta gene as such is not a risk factor contributing to DR4/DQ8-associated susceptibility. |
| 30 | 1448547 | One-hundred and seventy-two normotensive, insulin-dependent diabetic patients without clinical proteinuria (Albustix negative) were typed for the major histocompatibility complex class I (HLA-A, -B) and class II (HLA-DR) antigens. |
| 31 | 1448547 | There was no significant association between UA/UC and HLA-B8, -B15, -DR3, -DR4 or other antigens. |
| 32 | 1451952 | DR3,4 heterozygosity identified higher risk (16% after 8 years, 12% by age 22 years, p less than 10(-5)) than HLA-identity (10% and 7%, respectively, p less than 0.01); risks for DR3 or DR4 positive and for haplo-identical siblings were low (4%, 3% and 4.4%, respectively, NS). |
| 33 | 1478368 | DR2 antigen was found with decreased frequency in patients whereas no DR3/DR4 heterozygotes were observed. |
| 34 | 1485950 | Susceptibility to insulin-dependent diabetes mellitus (IDDM) correlates with the absence of aspartic acid in position 57 of the DQB1 and/or the presence of arginine in position 52 of the DQA1. |
| 35 | 1485950 | Two-thirds of these combinations were explained by DR3,DR4 heterozygotes. |
| 36 | 1485950 | These findings, together with the fact that the lowest frequency of DR3,DR4 heterozygosity (21%) was seen in Finland, show that heterozygosity for DQ and DR cannot explain the differences seen in IDDM incidence. |
| 37 | 1485950 | Susceptibility to insulin-dependent diabetes mellitus (IDDM) correlates with the absence of aspartic acid in position 57 of the DQB1 and/or the presence of arginine in position 52 of the DQA1. |
| 38 | 1485950 | Two-thirds of these combinations were explained by DR3,DR4 heterozygotes. |
| 39 | 1485950 | These findings, together with the fact that the lowest frequency of DR3,DR4 heterozygosity (21%) was seen in Finland, show that heterozygosity for DQ and DR cannot explain the differences seen in IDDM incidence. |
| 40 | 1502499 | It is well known that certain genes in the HLA-D region confer increased susceptibility to insulin-dependent diabetes mellitus (IDDM). |
| 41 | 1502499 | Previous studies have documented an increased risk associated with the HLA-DR beta chain alleles, DR3 and DR4, and the DQ beta chain allele DQB1*0302 (formerly DQw8). |
| 42 | 1548146 | Complementation of HLA-DQA and -DQB genes confers susceptibility and protection to insulin-dependent diabetes mellitus. |
| 43 | 1548146 | Lack of an aspartic acid 57 in the HLA-DQ beta chain was introduced as a genetic marker of insulin-dependent diabetes mellitus (IDDM). |
| 44 | 1548146 | The new susceptibility genotype DQA3-DQB3.2/DQA4.1-DQB2 (DQA1*0301-DQB1*0302/DQA1*0501-DQB1*0201) may explain the well-known excess of DR3/DR4 heterozygous IDDM patients and is expected to help identify individuals at risk for developing the disease. |
| 45 | 1576360 | HLA-antigens in Italian type 1 diabetic patients: role of DR3/DR4 antigens and breast feeding in the onset of the disease. |
| 46 | 1576360 | HLA-A, B, C, DR and DQ typing was performed in 381 Italian insulin-dependent diabetic patients and in 905 normal Italian subjects. |
| 47 | 1576360 | The diabetic patients had significantly higher frequencies of HLA-Cw7, B8, B18, DR3, DR4, DQw2 and DQw3 and significantly lower frequencies of HLA-B17, Bw51, DR2, DR7 and DRw11. |
| 48 | 1576360 | HLA-antigens in Italian type 1 diabetic patients: role of DR3/DR4 antigens and breast feeding in the onset of the disease. |
| 49 | 1576360 | HLA-A, B, C, DR and DQ typing was performed in 381 Italian insulin-dependent diabetic patients and in 905 normal Italian subjects. |
| 50 | 1576360 | The diabetic patients had significantly higher frequencies of HLA-Cw7, B8, B18, DR3, DR4, DQw2 and DQw3 and significantly lower frequencies of HLA-B17, Bw51, DR2, DR7 and DRw11. |
| 51 | 1628763 | It has been proposed that this difference in susceptibility depends on the absence (in the DR3 and DR4 haplotypes) or the presence (in the DR2 haplotype) of Asp57 in the DQ beta-chain. |
| 52 | 1633634 | The association of insulin-dependent diabetes mellitus and HLA began with weak associations of Class I antigens (B8 and B15) and progressed to Class II antigens (DR3 and DR4), then to subtypes of DR4 (Dw4, 10, and 14), and now to DQ molecules including the absence of aspartic acid at position 57 of the DQ beta chain and the presence of arginine at position 52 of the DQ alpha chain. |
| 53 | 1633634 | In rheumatoid arthritis (RA) the HLA antigen association remains with certain Class II molecules of the DR series (DR4 and DR1) that share amino acid sequences with a restricted number of other DR antigens seen in RA, as well as a segment of the gp 110 protein of the Epstein-Barr virus. |
| 54 | 1633634 | The association of insulin-dependent diabetes mellitus and HLA began with weak associations of Class I antigens (B8 and B15) and progressed to Class II antigens (DR3 and DR4), then to subtypes of DR4 (Dw4, 10, and 14), and now to DQ molecules including the absence of aspartic acid at position 57 of the DQ beta chain and the presence of arginine at position 52 of the DQ alpha chain. |
| 55 | 1633634 | In rheumatoid arthritis (RA) the HLA antigen association remains with certain Class II molecules of the DR series (DR4 and DR1) that share amino acid sequences with a restricted number of other DR antigens seen in RA, as well as a segment of the gp 110 protein of the Epstein-Barr virus. |
| 56 | 1676704 | It has been found that: 1) DQA2 (U allele) is not a susceptibility factor, 2) non-aspartic acid homozygosity in residue 57 (Asp 57 negative) of the DQ beta chains is positively correlated with insulin-dependent diabetes mellitus (IDDM), and 3) DQ beta Asp-57-negative and DQ alpha arginine-52-positive (Arg-52-positive) individuals are increased among diabetic patients; this latter analysis shows a higher etiologic fraction (delta) value than the one obtained when considering only homozygous DQ beta Asp-57-negative individuals. |
| 57 | 1676704 | These data do not discard the possibility that DR3/DR4 may contain the primary susceptibility factors. |
| 58 | 1682241 | The combination of the HLA complement allotypes BFS, C2C, C4AQ0 (deleted gene) and C4B1, termed SC01 complotype, usually present in the HLA-B8,DR3,DQw2 diabetogenic haplotype, has also been found in a novel "low frequency" HLA-B49,DR4,DQw8 haplotype associated with Spanish insulin-dependent diabetes mellitus (IDDM). |
| 59 | 1682241 | On the other hand, HLA-B49,SC01,DR4 is the first DR4-bearing IDDM-susceptible haplotype with a deleted C4 gene described so far and the only DR4-bearing haplotype found in the Spanish population. |
| 60 | 1685266 | Eighteen unrelated Chinese patients with insulin-dependent diabetes mellitus (IDDM) were analyzed for HLA Class II genes using a variety of molecular biological techniques including restriction fragment length polymorphism (RFLP), polymerase chain reaction with allele-specific oligonucleotides (PCR-ASO) and direct DNA sequencing. |
| 61 | 1685266 | The high frequency of DR3/DR4 heterozygotes found in the Chinese with IDDM strengthens the importance of this combination of haplotypes in IDDM susceptibility since it is present in two genetically distant populations--Chinese and Caucasians. |
| 62 | 1688161 | Heterozygous siblings who carried both DR3DQw2 and DR4DQw8 subtypes disclosed a highly increased risk and more than 80% of DR3/DR4 affected siblings received a paternal DR4DQw8 together with a maternal DR3DQw2. |
| 63 | 1750745 | HLA typing studies demonstrated a high prevalence of DR3 and DR4 alleles and especially of simultaneous expression of both these alleles. |
| 64 | 1783573 | DR4-related autoimmune disorders such as rheumatoid arthritis (RA) and insulin-dependent diabetes mellitus (IDDM) are virtually unknown in indigenous populations of Australia and Oceania and this study confirmed that high-risk RA determinants, Dw4 and Dw14, occurred rarely. |
| 65 | 1852994 | Ninety percent of IDD belong to the DR3 or DR4 group. |
| 66 | 1890017 | To ascertain why HLA-DR2 seems to confer only a moderate resistance to insulin-dependent diabetes mellitus (IDDM) in the high-incidence population of Sardinia, Italy, 32 families having one individual affected with IDDM (the proband) and 31 families without IDDM history were randomly selected from the same geographical area and serologically and molecularly HLA typed. |
| 67 | 1890017 | However, a stratified analysis performed by removing the DR3 and DR4 haplotypes showed that the frequency of this haplotype is significantly increased in IDDM patients. |
| 68 | 1908143 | Distribution of HLA-DRB1, -DQA1 and -DQB1 alleles and DQA1-DQB1 genotypes among Norwegian patients with insulin-dependent diabetes mellitus. |
| 69 | 1908143 | We have studied 87 unrelated Caucasian insulin-dependent diabetes mellitus (IDDM) patients and 181 healthy controls by oligotyping for 20 DRB1, eight DQA1 and 13 DQB1 alleles, and established their DR-DQ haplotypes and DQ genotypes. |
| 70 | 1908143 | An increase of DRB1 alleles encoding DR4 was found among IDDM patients, but the distribution of DR4 subtypes did not differ among DR4-positive IDDM patients and controls. |
| 71 | 1916001 | Studies of various insulin-dependent diabetes mellitus (IDDM) populations have shown that certain HLA antigens confer a high risk of developing disease. |
| 72 | 1916001 | DR3/DR4, although more frequent, did not achieve statistical significance. |
| 73 | 1930940 | The aetiology of insulin-dependent diabetes (IDDM) involves genetic predisposition, a major component of which has been mapped in the HLA complex, near to or identical with genes encoding class II molecules. |
| 74 | 1930940 | The particularly high risk of DR3/DR4 heterozygotes suggests that susceptibility is determined by two genes acting synergistically. |
| 75 | 1972363 | A significant increase in the frequency of DPw3/6 alleles defined by restriction-fragment-length polymorphism is observed in insulin-dependent diabetes mellitus (IDDM) patients relative to healthy control subjects (34.6 vs. 10.5%, P less than 0.009). |
| 76 | 1972363 | Log-linear modeling demonstrates that this association is independent of HLA-DR3 and -DR4 and IDDM association and cannot be attributed to linkage disequilibrium between HLA-DP and -DR. |
| 77 | 1972363 | The strength of the DPw3/6 association is not significantly less than that of either DR3 or DR4. |
| 78 | 1972363 | A significant increase in the frequency of DPw3/6 alleles defined by restriction-fragment-length polymorphism is observed in insulin-dependent diabetes mellitus (IDDM) patients relative to healthy control subjects (34.6 vs. 10.5%, P less than 0.009). |
| 79 | 1972363 | Log-linear modeling demonstrates that this association is independent of HLA-DR3 and -DR4 and IDDM association and cannot be attributed to linkage disequilibrium between HLA-DP and -DR. |
| 80 | 1972363 | The strength of the DPw3/6 association is not significantly less than that of either DR3 or DR4. |
| 81 | 1995752 | Frequencies of DR3 and DR4 were significantly increased in both the diabetics and their unaffected siblings relative to the general population and DR2 was decreased. |
| 82 | 1995752 | Forty-six percent of diabetic children possessed both DR3 and DR4 antigens while only 7% had neither. |
| 83 | 1995752 | The findings are consistent with those in other geographical areas and give strong support to the role of DR3 and DR4 antigens as markers for diabetes susceptibility genes. |
| 84 | 1995752 | Frequencies of DR3 and DR4 were significantly increased in both the diabetics and their unaffected siblings relative to the general population and DR2 was decreased. |
| 85 | 1995752 | Forty-six percent of diabetic children possessed both DR3 and DR4 antigens while only 7% had neither. |
| 86 | 1995752 | The findings are consistent with those in other geographical areas and give strong support to the role of DR3 and DR4 antigens as markers for diabetes susceptibility genes. |
| 87 | 1995752 | Frequencies of DR3 and DR4 were significantly increased in both the diabetics and their unaffected siblings relative to the general population and DR2 was decreased. |
| 88 | 1995752 | Forty-six percent of diabetic children possessed both DR3 and DR4 antigens while only 7% had neither. |
| 89 | 1995752 | The findings are consistent with those in other geographical areas and give strong support to the role of DR3 and DR4 antigens as markers for diabetes susceptibility genes. |
| 90 | 1996407 | HLA-class III region genes may be associated with susceptibility to insulin-dependent diabetes mellitus (IDDM). |
| 91 | 1996407 | In this study an NcoI polymorphism of the tumour necrosis factor beta (TNF-beta) gene, which is positioned next to the tumour necrosis factor alpha (TNF-alpha) gene in the HLA class III region, was detected by restriction fragment length polymorphism (RFLP). |
| 92 | 1996407 | In all groups there was a haplotype assignment of the TNF-beta 5.5-kb allele to B8,DR3 haplotypes, and of the TNF-beta 10.5-kb allele to B15,DR4-positive haplotypes. |
| 93 | 1996407 | The allelic and genotypic frequencies differed between DR3,4 IDDM patients and DR3,4 controls, and the DR3,4 control group differed significantly from the randomly selected control group (P less than 0.0079). |
| 94 | 1996407 | In HLA-DR3,4- and DQw8-positive persons, the DR3 haplotypes carried the 10.5-kb allele three times more frequently in IDDM patients than in controls, suggesting that the 10.5-kb allele when present on DR3 haplotypes may contribute to susceptibility to IDDM in DR3,4 heterozygous individuals. |
| 95 | 1996407 | A contributory role of the 10.5-kb allele in genetic IDDM susceptibility was supported by the sibpair analysis, in which all were TNF-beta identical. |
| 96 | 1996407 | Twenty-five healthy and eight newly diagnosed IDDM patients were randomly selected to study the Escherichia coli lipopolysaccharides (LPS)-purified protein derivate (tuberculin) (PPD)-, and phytohaemagglutinin (PHA)-stimulated monocyte (Mo) secretions of interleukin 1 beta (IL-1 beta) and TNF-alpha in relation to the NcoI TNF-beta gene polymorphism. |
| 97 | 1996407 | The LPS- and PHA-stimulated Mo IL-1 beta and TNF-alpha secretions were significantly lower for the TNF-beta 5.5/10.5 kb heterozygous individuals than for TNF-beta 10.5 kb homozygous individuals. |
| 98 | 1996407 | Furthermore, the Mo IL-1 beta and TNF-alpha secretions of IDDM patients were significantly higher than the Mo secretions of TNF-beta genotype-matched healthy controls. |
| 99 | 1996407 | This study suggests an association between the 10.5 kb TNF-beta allele and IDDM, and demonstrates an association between monokine responses and TNF-beta genotypes. |
| 100 | 2006934 | Insulin-dependent diabetes mellitus is associated with an increased frequency of certain histocompatibility antigens located on chromosome six, the most common types being B-8, B-15, DR-3, DR-4, and DR-7. |
| 101 | 2045289 | The mode of inheritance of the DR3- and DR4-associated susceptibility genotype is essentially recessive, based on both the segregation data and the existence of Hardy-Weinberg equilibrium in Ashkenazi Jewish and possibly in patients of other populations. 2. |
| 102 | 2069353 | The mechanism of pancreatic beta-cell destruction in type I (insulin-dependent) diabetes mellitus (IDDM) involves autoimmune events directed against these cells. |
| 103 | 2069353 | HLA alleles associated with IDDM include DR3 and DR4, with the risk of IDDM being especially high in individuals with the heterozygous combination DR3/DR4. |
| 104 | 2075784 | The frequency of HLA-B18, DR3 and DR4 antigens was significantly increased whereas DR2, DR5 and DR7 were decreased in comparison with 189 healthy unrelated controls without family history of diabetes. |
| 105 | 2075784 | We found no statistically significant relationship between HLA antigens and the other variables studied including the presence of islet cell antibodies, complement fixing islet cell antibodies, insulin autoantibodies, organ-specific antibodies, fasting and maximal glucagon stimulated C-peptide levels, initial glycemia and glycosylated hemoglobin. |
| 106 | 2096182 | Insulin-dependent diabetes mellitus (IDDM) is associated with several DR3- or DR4-containing ancestral haplotypes (AHs). |
| 107 | 2096182 | The MHC contains several regions of potential interest in relation to susceptibility to IDDM; these may explain the association with only certain DR3- and DR4-carrying AH and DR3,4 heterozygosity in terms of cis and trans interactions. |
| 108 | 2096182 | Insulin-dependent diabetes mellitus (IDDM) is associated with several DR3- or DR4-containing ancestral haplotypes (AHs). |
| 109 | 2096182 | The MHC contains several regions of potential interest in relation to susceptibility to IDDM; these may explain the association with only certain DR3- and DR4-carrying AH and DR3,4 heterozygosity in terms of cis and trans interactions. |
| 110 | 2101347 | HLA class I and class II antigens were studied in 97 unrelated IDDM patients, 33 complete families with at least one affected member each, and 559 healthy controls. |
| 111 | 2101347 | The genotype analysis of the patients showed a strong increase of the DR3/DR4 heterozygotes with a relative risk higher than that of the DR3 and DR4 homozygotes. |
| 112 | 2187461 | Supratypes and ancestral haplotypes in IDDM: potential importance of central non-HLA MHC genes. |
| 113 | 2187461 | This approach avoids the confusion which has resulted from using DR3 or DR4 which are only sometimes associated with the relevant genes. |
| 114 | 2190442 | UAE values were positively correlated with age, GH secretion, but not with duration of disease, glycosylated hemoglobin, renal size or N-acetyl-beta-glucosaminidase excretion. |
| 115 | 2190442 | HLA DR3/DR4 heterozygosity frequency was significantly higher (p less than 0.01) in the microalbuminuric group than in the normoalbuminuric. |
| 116 | 2190442 | HLA DR3/DR4 heterozygosity, onset of disease at puberty and higher GH values, the probability of developing abnormal levels of UAE will increase. |
| 117 | 2190442 | UAE values were positively correlated with age, GH secretion, but not with duration of disease, glycosylated hemoglobin, renal size or N-acetyl-beta-glucosaminidase excretion. |
| 118 | 2190442 | HLA DR3/DR4 heterozygosity frequency was significantly higher (p less than 0.01) in the microalbuminuric group than in the normoalbuminuric. |
| 119 | 2190442 | HLA DR3/DR4 heterozygosity, onset of disease at puberty and higher GH values, the probability of developing abnormal levels of UAE will increase. |
| 120 | 2204051 | Distinct relationship of antigens DR3 and DR4 with a clinical course of disease and its severity was undetectable. |
| 121 | 2254897 | An increased frequency of HLA-B8, DR3 and DR4 in patients with insulin dependent diabetes mellitus (IDDM) compared to controls and patients with noninsulin dependent diabetes mellitus (NIDDM) was confirmed. |
| 122 | 2254897 | No correlation was found between DR3, DR4 and limited joint mobility or diabetic complications. |
| 123 | 2254897 | An increased frequency of HLA-B8, DR3 and DR4 in patients with insulin dependent diabetes mellitus (IDDM) compared to controls and patients with noninsulin dependent diabetes mellitus (NIDDM) was confirmed. |
| 124 | 2254897 | No correlation was found between DR3, DR4 and limited joint mobility or diabetic complications. |
| 125 | 2266274 | No significant differences in the frequencies of DR3, DR4, or DR2 were found between patients with insulin-dependent diabetes and patients with normal glucose tolerance or between any of these groups and controls. |
| 126 | 2298852 | HLA-DR3 or -DR4 segregation distortion to normal or insulin-dependent (ID) diabetic offspring of 108 Spanish families whose parents were healthy was not observed; however, DR3 or DR4 ID offspring is significantly increased in the present study, since parents were chosen after tracing ID children. |
| 127 | 2298852 | Thus, ethnic group differences in a genetic (T/t-like) or metabolic mechanism might confer advantages to DR3- or DR4-bearing gametes from ID diabetic parents, but segregation distortion might only affect certain HLA DR3 or DR4 extended haplotypes which are frequent and characteristic for certain ethnic groups (i.e. |
| 128 | 2298852 | HLA-DR3 or -DR4 segregation distortion to normal or insulin-dependent (ID) diabetic offspring of 108 Spanish families whose parents were healthy was not observed; however, DR3 or DR4 ID offspring is significantly increased in the present study, since parents were chosen after tracing ID children. |
| 129 | 2298852 | Thus, ethnic group differences in a genetic (T/t-like) or metabolic mechanism might confer advantages to DR3- or DR4-bearing gametes from ID diabetic parents, but segregation distortion might only affect certain HLA DR3 or DR4 extended haplotypes which are frequent and characteristic for certain ethnic groups (i.e. |
| 130 | 2384193 | The gene frequencies, haplotype relative risks, and zygotic assortments of HLA-DR in three ethnically defined samples of insulin-dependent diabetes mellitus (IDDM) patients were determined in a prospective family study. |
| 131 | 2384193 | Although DR3 and DR4 were positively associated with IDDM in the probands of 123 northern European, 94 Ashkenazi Jewish, and 49 New York Hispanic families, significant excess of DR*3/4 heterozygotes was observed only among the probands from families of northern European ancestry. |
| 132 | 2401398 | We analysed the inheritance of DR3 and DR4 haplotypes from the father or mother (DR3p, DR4p, DR3m and DR4m, respectively), in the index cases and in the affected and non-affected siblings of 246 diabetic simplex and 41 multiplex families without affected parents. |
| 133 | 2401398 | Among the DR3,4 positive index cases and affected siblings, the paternal and maternal DR3 and DR4 antigens were not distributed randomly: 62% and 72%, respectively, had received DR4 from their father and DR3 from their mother (DR4p/DR3m), while only 38% and 28%, respectively, had received a paternal DR3 together with a maternal DR4 (DR3p/DR4m). |
| 134 | 2401398 | We analysed the inheritance of DR3 and DR4 haplotypes from the father or mother (DR3p, DR4p, DR3m and DR4m, respectively), in the index cases and in the affected and non-affected siblings of 246 diabetic simplex and 41 multiplex families without affected parents. |
| 135 | 2401398 | Among the DR3,4 positive index cases and affected siblings, the paternal and maternal DR3 and DR4 antigens were not distributed randomly: 62% and 72%, respectively, had received DR4 from their father and DR3 from their mother (DR4p/DR3m), while only 38% and 28%, respectively, had received a paternal DR3 together with a maternal DR4 (DR3p/DR4m). |
| 136 | 2405478 | The mechanism of pancreatic B-cell destruction in type I (insulin-dependent) diabetes (IDDM) involves autoimmune phenomena based on genetic predisposition. |
| 137 | 2405478 | The genetic susceptibility is distinguished by increased frequency of the HLA antigens DR3 and DR4 and particularly their heterozygous combination DR3/DR4. |
| 138 | 2451692 | HLA-DR (DR3, DR4, and DR5) and HLA-DQ (DQw2/DQw3) Ag can restrict these T cell responses to human insulin epitopes. |
| 139 | 2499498 | Analysis of HLA haplotypes occurring in more than one, only one, or no diabetics in GAW5 multiplex insulin-dependent diabetes mellitus (IDDM) families suggested: 1) DR3, DR4, DRw6, and DRw8 are positively associated, and DR2 is negatively associated, with IDDM; 2) DR4 haplotypes are more diabetogenic than DR3 haplotypes; some DR3 haplotypes lacking B8/B18 are more diabetogenic than those carrying B8/B18; DR3 haplotypes with DR beta TaqI bands [2,5,10/11] are more diabetogenic than those without; DR4 haplotypes that carry DQw3.2 are more diabetogenic than those that do not; some DR2 haplotypes are diabetogenic rather than protective. |
| 140 | 2499498 | Analysis of DR3 and DR4 transmission from DR3/X and DR4wX (X not equal to 3,4) healthy parents suggested: 3) no distortion of transmission to healthy children and 4) mothers transmit DR4 (and perhaps DR3) less often than fathers to diabetic children. |
| 141 | 2499498 | Analysis of HLA haplotypes occurring in more than one, only one, or no diabetics in GAW5 multiplex insulin-dependent diabetes mellitus (IDDM) families suggested: 1) DR3, DR4, DRw6, and DRw8 are positively associated, and DR2 is negatively associated, with IDDM; 2) DR4 haplotypes are more diabetogenic than DR3 haplotypes; some DR3 haplotypes lacking B8/B18 are more diabetogenic than those carrying B8/B18; DR3 haplotypes with DR beta TaqI bands [2,5,10/11] are more diabetogenic than those without; DR4 haplotypes that carry DQw3.2 are more diabetogenic than those that do not; some DR2 haplotypes are diabetogenic rather than protective. |
| 142 | 2499498 | Analysis of DR3 and DR4 transmission from DR3/X and DR4wX (X not equal to 3,4) healthy parents suggested: 3) no distortion of transmission to healthy children and 4) mothers transmit DR4 (and perhaps DR3) less often than fathers to diabetic children. |
| 143 | 2499501 | Analysis of the Fifth Genetic Analysis Workshop (GAW5) insulin-dependent diabetes mellitus (IDDM) data leads to the following conclusions: 1) With a maximum-likelihood affected sib pair method, there is strong evidence for linkage with HLA and no evidence for linkage with INS, Gm, or Km. 2) Susceptibility as defined by HLA genotypes is very complex. |
| 144 | 2499501 | Each DR allele has a unique susceptibility, and DR3 and DR4 haplotype associations for DR 3/4 genotypes are different from those for 3/X and 4/X. 3) Risk is substantially higher in sibships with an affected father compared to those with an affected mother. |
| 145 | 2499506 | Characteristics of a multiplex sample of families with insulin-dependent diabetes mellitus (IDDM) are studied and contrasted with similar characteristics in other, more conventionally sampled data sets. |
| 146 | 2499506 | "Control" haplotypes, i.e., those not transmitted to the first affected offspring, had a higher frequency of DR3 and DR4 than expected, and a rather high frequency of affected parents was observed. |
| 147 | 2508996 | Among 285 caucasoid families genotyped for HLA-A, B, C, DR including at least one insulin-dependent diabetic child, we have studied the effect of the DR3 and DR4 antigens inherited from the father or the mother (DR3p, DR3m, DR4p and DR4m, respectively) on the recurrence of the disease among siblings; families with affected parents being excluded, a total of 37 affected and 200 non affected siblings have been taken into consideration. |
| 148 | 2508996 | Among the DR3, DR4 positive siblings, the DR4p/DR3m genotype was observed at a greater frequency than the DR3p/DR4m genotype among affected, but not among unaffected siblings. |
| 149 | 2508996 | Among 285 caucasoid families genotyped for HLA-A, B, C, DR including at least one insulin-dependent diabetic child, we have studied the effect of the DR3 and DR4 antigens inherited from the father or the mother (DR3p, DR3m, DR4p and DR4m, respectively) on the recurrence of the disease among siblings; families with affected parents being excluded, a total of 37 affected and 200 non affected siblings have been taken into consideration. |
| 150 | 2508996 | Among the DR3, DR4 positive siblings, the DR4p/DR3m genotype was observed at a greater frequency than the DR3p/DR4m genotype among affected, but not among unaffected siblings. |
| 151 | 2515413 | A simple correlation between IDDM and residue 57 of the DQ beta chain does not hold in Oriental IDDM patients, cannot account for DR3,DR4 synergism and does not explain different modes of inheritance of DR3- and DR4-related IDDM determinants. |
| 152 | 2564383 | An increased risk of insulin-dependent diabetes mellitus (IDDM) among HLA-DR4,DQw8/DRw8,DQw4 heterozygotes. |
| 153 | 2564383 | Serological HLA typing of 92 insulin-dependent diabetes mellitus (IDDM) patients and 300 healthy controls was performed by the immunomagnetic typing technique. |
| 154 | 2564383 | We found an increased risk of IDDM among DR4/w8 heterozygotes, similar to that seen for DR3/4 heterozygotes. |
| 155 | 2564383 | Therefore, eight of nine DR4/w8 IDDM patients seemed to be DR4,DQw8/DRw8,DQw4, which, thus, may be associated with susceptibility to develop IDDM. |
| 156 | 2564383 | An increased risk of insulin-dependent diabetes mellitus (IDDM) among HLA-DR4,DQw8/DRw8,DQw4 heterozygotes. |
| 157 | 2564383 | Serological HLA typing of 92 insulin-dependent diabetes mellitus (IDDM) patients and 300 healthy controls was performed by the immunomagnetic typing technique. |
| 158 | 2564383 | We found an increased risk of IDDM among DR4/w8 heterozygotes, similar to that seen for DR3/4 heterozygotes. |
| 159 | 2564383 | Therefore, eight of nine DR4/w8 IDDM patients seemed to be DR4,DQw8/DRw8,DQw4, which, thus, may be associated with susceptibility to develop IDDM. |
| 160 | 2567257 | HLA and insulin gene associations with IDDM. |
| 161 | 2567257 | The HLA DR genotype frequencies in insulin-dependent diabetes mellitus (IDDM) patients and the frequencies of DR alleles transmitted from affected parent to affected child both indicate that the DR3-associated predisposition is more "recessive" and the DR4-associated predisposition more "dominant" in inheritance after allowing for the DR3/DR4 synergistic effect. |
| 162 | 2567257 | B locus distributions on patient haplotypes indicate that only subsets of both DR3 and DR4 are predisposing. |
| 163 | 2567257 | Heterogeneity is detected for both the DR3 and DR4 predisposing haplotypes based on DR genotypic class. |
| 164 | 2567257 | HLA and insulin gene associations with IDDM. |
| 165 | 2567257 | The HLA DR genotype frequencies in insulin-dependent diabetes mellitus (IDDM) patients and the frequencies of DR alleles transmitted from affected parent to affected child both indicate that the DR3-associated predisposition is more "recessive" and the DR4-associated predisposition more "dominant" in inheritance after allowing for the DR3/DR4 synergistic effect. |
| 166 | 2567257 | B locus distributions on patient haplotypes indicate that only subsets of both DR3 and DR4 are predisposing. |
| 167 | 2567257 | Heterogeneity is detected for both the DR3 and DR4 predisposing haplotypes based on DR genotypic class. |
| 168 | 2573447 | The segregation pattern of hybridizing fragments showed that: (1) for each of the DR2, DR3, and DR4 specificities, two different alleles can be identified by the DQ beta probe; (2) a 1.9 kb-Taq 1 fragment with the DR4 specificity and a 6.0 kb-Taq-1 fragment within the DR2 specificity tend to cosegregate with IDDM; (3) there was no preferential segregation of the two alleles detected within the DR3 specificity (one allele identified by a 4.7 kb-Taq 1 fragment is quite common among individuals with the DR3 specificity). |
| 169 | 2617513 | DQw8 (DQw3.2) on DR4 haplotypes is a susceptibility gene for development of insulin-dependent diabetes mellitus (IDDM) in Caucasoids, possibly because it encodes a non-Asp amino acid (aa) (i.e. |
| 170 | 2617513 | We have examined 14 Japanese IDDM patients, selected to be either DR4 or DRw9 (associated to IDDM among Japanese). |
| 171 | 2617513 | DQw8 (DQw3.2) on DR4 haplotypes is a susceptibility gene for development of insulin-dependent diabetes mellitus (IDDM) in Caucasoids, possibly because it encodes a non-Asp amino acid (aa) (i.e. |
| 172 | 2617513 | We have examined 14 Japanese IDDM patients, selected to be either DR4 or DRw9 (associated to IDDM among Japanese). |
| 173 | 2622285 | In diabetic patients, DR3 and DR4 were found in 85% and 63% respectively (p less than 0.001). |
| 174 | 2629160 | Thirty Ethiopian malnutrition-related diabetes mellitus (MRDM) patients were HLA typed and their HLA antigen frequencies were compared to those of 31 previously typed insulin-dependent diabetes mellitus (IDDM) patients and to 84 controls from the same ethnic background. |
| 175 | 2629160 | In comparison to IDDM that is associated with both DR3 and DR4 in this population, MRDM showed no significant differences in HLA class II antigens frequencies. |
| 176 | 2645741 | HLA determinations in these patients showed absence of DR3 and DR4, and presence of DR2. |
| 177 | 2648900 | [HLA, A, B, C, DR, C4, Bf in insulin-dependent diabetics in the Tunisian population]. |
| 178 | 2648900 | The frequency of HLA-A-B and DR antigens as well as the Bf and C4 allotypes have been investigated in insulinodependant diabetes mellitus (IDDM) and compared to that of healthy controls in Tunisian population. |
| 179 | 2648900 | An increase of A30, DR3, DR4, BfF1, C4AQ0 and C4BQ0 and decrease of B40, DR2, DR5 and DR6 were found in diabetes when compared to the value observation controls. |
| 180 | 2648900 | The strongest association was noticed with HLA, DR3 and DR4. |
| 181 | 2648900 | [HLA, A, B, C, DR, C4, Bf in insulin-dependent diabetics in the Tunisian population]. |
| 182 | 2648900 | The frequency of HLA-A-B and DR antigens as well as the Bf and C4 allotypes have been investigated in insulinodependant diabetes mellitus (IDDM) and compared to that of healthy controls in Tunisian population. |
| 183 | 2648900 | An increase of A30, DR3, DR4, BfF1, C4AQ0 and C4BQ0 and decrease of B40, DR2, DR5 and DR6 were found in diabetes when compared to the value observation controls. |
| 184 | 2648900 | The strongest association was noticed with HLA, DR3 and DR4. |
| 185 | 2669340 | An association of diabetes mellitus type I with HLA-B8, DR3 and DR4 was found. |
| 186 | 2676279 | During the last 25 years the concept of a chronic autoimmune process leading to the development of insulin dependent diabetes (IDD) has emerged. |
| 187 | 2676279 | The initial description of linkage disequilibrium of HLA DR3 and DR4 alleles with IDD has now progressed to the molecular level with the identification of residue 57 of the HLA DQ beta chain as crucial to the genetic predisposition to IDD. |
| 188 | 2676279 | However, some therapies in the animal models, not typically considered immunologic, such as protein restriction and insulin therapy, have prevented IDD. |
| 189 | 2681635 | All five subjects with islet cell antibodies or human leukocyte antigen DR3/DR4 with initial impaired glucose tolerance have either acquired diabetes or have abnormal glucose tolerance. |
| 190 | 2681635 | We conclude that in the absence of islet cell antibodies or human leukocyte antigen DR3/DR4 heterozygosity, incidental hyperglycemia or glycosuria is unlikely to be associated with progression or diabetes. |
| 191 | 2681635 | All five subjects with islet cell antibodies or human leukocyte antigen DR3/DR4 with initial impaired glucose tolerance have either acquired diabetes or have abnormal glucose tolerance. |
| 192 | 2681635 | We conclude that in the absence of islet cell antibodies or human leukocyte antigen DR3/DR4 heterozygosity, incidental hyperglycemia or glycosuria is unlikely to be associated with progression or diabetes. |
| 193 | 2689194 | Serological HLA studies have shown susceptibility to type 1 diabetes is linked to HLA DR3 and DR4 allels, whereas DR2 and DR5 alleles contain protective elements. |
| 194 | 2698733 | Studies of patients with insulin-dependent diabetes and their families have shown increased incidences of HLA markers B8, B15, DR3 and DR4. |
| 195 | 2701766 | Autoimmune nature of Type 1 diabetes is based on: association with genetic markers of histocompatibility mainly with the DR3 and DR4 haplotypes of the HLA system; anomalies of the humoral and cellular immunity present in a significant percentage of Type 1 diabetic patients, its association with other autoimmune diseases; the histological features of the affected pancreas and the prevention of experimental diabetes by immunosuppression. |
| 196 | 2714046 | The frequency of HLA A, B, and DR antigens as well as the Bf and C4 allotypes have been investigated in insulin-dependent diabetes mellitus (IDDM) and compared to that of healthy controls in the Tunisian population. |
| 197 | 2714046 | An increase of A30, DR3, DR4, BfF1, C4Ao, and C4Bo and decrease of B40, DR2, DR5, and DR6 were found in diabetics when compared to the value observed in controls. |
| 198 | 2714046 | The strongest association was noticed with HLA DR3 and DR4. |
| 199 | 2714046 | Heterozygotes DR3 DR4 were very frequent in diabetics: 24.2 per cent versus 3.6 per cent in controls (relative risk 7.72). |
| 200 | 2714046 | The frequency of HLA A, B, and DR antigens as well as the Bf and C4 allotypes have been investigated in insulin-dependent diabetes mellitus (IDDM) and compared to that of healthy controls in the Tunisian population. |
| 201 | 2714046 | An increase of A30, DR3, DR4, BfF1, C4Ao, and C4Bo and decrease of B40, DR2, DR5, and DR6 were found in diabetics when compared to the value observed in controls. |
| 202 | 2714046 | The strongest association was noticed with HLA DR3 and DR4. |
| 203 | 2714046 | Heterozygotes DR3 DR4 were very frequent in diabetics: 24.2 per cent versus 3.6 per cent in controls (relative risk 7.72). |
| 204 | 2714046 | The frequency of HLA A, B, and DR antigens as well as the Bf and C4 allotypes have been investigated in insulin-dependent diabetes mellitus (IDDM) and compared to that of healthy controls in the Tunisian population. |
| 205 | 2714046 | An increase of A30, DR3, DR4, BfF1, C4Ao, and C4Bo and decrease of B40, DR2, DR5, and DR6 were found in diabetics when compared to the value observed in controls. |
| 206 | 2714046 | The strongest association was noticed with HLA DR3 and DR4. |
| 207 | 2714046 | Heterozygotes DR3 DR4 were very frequent in diabetics: 24.2 per cent versus 3.6 per cent in controls (relative risk 7.72). |
| 208 | 2731409 | Highly significant association of HLA, A1, B8, DR3, and DR4 were found in patients with IDDM as compared to normal individuals. |
| 209 | 2758954 | The study of HLA histocompatibility antigens and insulin-dependent diabetes mellitus (IDDM) in non-White populations may provide a unique opportunity to more accurately define the diabetes susceptibility gene(s) located within the HLA region. |
| 210 | 2758954 | Several common haplotypes (B8/DR3, B15/DR4) in the non-Hispanic White group occurred less frequently in the Mexican-American group. |
| 211 | 2758954 | Although both DR3- and DR4-haplotype frequencies differed significantly between the two groups, the relative frequency of DR3- but not DR4-containing haplotypes was similar in both ethnic groups. |
| 212 | 2758954 | This adds to the evidence suggesting that different susceptibilities are provided by the haplotypes carrying the DR3 and DR4 alleles. |
| 213 | 2758954 | The study of HLA histocompatibility antigens and insulin-dependent diabetes mellitus (IDDM) in non-White populations may provide a unique opportunity to more accurately define the diabetes susceptibility gene(s) located within the HLA region. |
| 214 | 2758954 | Several common haplotypes (B8/DR3, B15/DR4) in the non-Hispanic White group occurred less frequently in the Mexican-American group. |
| 215 | 2758954 | Although both DR3- and DR4-haplotype frequencies differed significantly between the two groups, the relative frequency of DR3- but not DR4-containing haplotypes was similar in both ethnic groups. |
| 216 | 2758954 | This adds to the evidence suggesting that different susceptibilities are provided by the haplotypes carrying the DR3 and DR4 alleles. |
| 217 | 2758954 | The study of HLA histocompatibility antigens and insulin-dependent diabetes mellitus (IDDM) in non-White populations may provide a unique opportunity to more accurately define the diabetes susceptibility gene(s) located within the HLA region. |
| 218 | 2758954 | Several common haplotypes (B8/DR3, B15/DR4) in the non-Hispanic White group occurred less frequently in the Mexican-American group. |
| 219 | 2758954 | Although both DR3- and DR4-haplotype frequencies differed significantly between the two groups, the relative frequency of DR3- but not DR4-containing haplotypes was similar in both ethnic groups. |
| 220 | 2758954 | This adds to the evidence suggesting that different susceptibilities are provided by the haplotypes carrying the DR3 and DR4 alleles. |
| 221 | 2784133 | HLA-DR4 is associated with insulin-dependent diabetes mellitus (IDDM) in many populations. |
| 222 | 2784133 | The only IDDM-associated DR4 haplotypes were those carrying the IDDM-associated alleles at both loci (RR = 12.1); haplotypes with Dw4 or 10 but not DQ3.2, or vice versa, had a RR less than 1. |
| 223 | 2801776 | Autoimmune thyroid phenomena are not evidence for human lymphocyte antigen-genetic heterogeneity in insulin-dependent diabetes. |
| 224 | 2801776 | It is well established that there is genetic heterogeneity between a human lymphocyte antigen (HLA)-DR3-associated allele and an HLA-DR4-associated allele in insulin-dependent diabetes mellitus (IDDM). |
| 225 | 2801776 | These results suggest that thyroid autoimmunity in IDDM is part of the IDDM "syndrome" and is associated with DR3 and DR4 to the same extent that IDDM without thyroid disease is associated with these two antigens. |
| 226 | 2801776 | Thus, although genetic studies are consistent with the heterogeneity between DR3 and DR4 in IDDM, there is no HLA-thyroid disease association to support this heterogeneity. |
| 227 | 2801776 | Autoimmune thyroid phenomena are not evidence for human lymphocyte antigen-genetic heterogeneity in insulin-dependent diabetes. |
| 228 | 2801776 | It is well established that there is genetic heterogeneity between a human lymphocyte antigen (HLA)-DR3-associated allele and an HLA-DR4-associated allele in insulin-dependent diabetes mellitus (IDDM). |
| 229 | 2801776 | These results suggest that thyroid autoimmunity in IDDM is part of the IDDM "syndrome" and is associated with DR3 and DR4 to the same extent that IDDM without thyroid disease is associated with these two antigens. |
| 230 | 2801776 | Thus, although genetic studies are consistent with the heterogeneity between DR3 and DR4 in IDDM, there is no HLA-thyroid disease association to support this heterogeneity. |
| 231 | 2863632 | To evaluate the role of Coxsackie B viruses in the pathogenesis of insulin-dependent (juvenile-onset, type 1) diabetes mellitus (IDDM), attempts were made to correlate virus-specific IgM responses with HLA genes, autoimmune responses, and C-peptide secretion. |
| 232 | 2863632 | HLA DR3, DR4, or both were present in 73 of 90 (81%) diabetic patients; 22 of 23 (96%) with Coxsackie-B-virus-specific IgM had at least one of these HLA types, compared with 51 of 67 (76%) without virus-specific IgM. |
| 233 | 2881884 | In contrast, the DQ3.DR4.b DQ beta haplotype was significantly decreased in IDD-associated DR4 chromosomes (P = 0.04). |
| 234 | 2901399 | HLA-DQ system and insulin-dependent diabetes mellitus in Japanese: does it contribute to the development of IDDM as it does in Caucasians? |
| 235 | 2901399 | Fifty-six unrelated Japanese patients with insulin-dependent diabetes mellitus (IDDM) were HLA-typed, and restriction fragment length polymorphism (RFLP) analysis was performed after enzyme digestion with Bam HI and Taq I by using both DR and DQ probes. |
| 236 | 2901399 | As previously reported, increased frequencies of Bw54, Cw1, DR4, and DRw53, which are in strong linkage disequilibrium in the Japanese population and make the characteristic Japanese haplotype, were confirmed. |
| 237 | 2951844 | Twelve insulin-dependent diabetes mellitus (IDDM) patients and healthy controls, who all carried the serologically defined DR3 and DR4 antigens, were compared with respect to other HLA polymorphisms. |
| 238 | 2951844 | Furthermore, when the distribution of all DQ beta-specific fragments which demonstrated polymorphism in our material was taken into account, nine of the 12 DR3, 4 IDDM patients demonstrated a similar DQ beta polymorphism compared with only two out of the 12 DR3, 4 controls (P = 0.006; corrected P = 0.037). |
| 239 | 2952412 | Fifty-six had islet cell antibodies and/or were heterozygous for HLA DR3 and DR4 (Group A) whereas 44 had neither of these markers (Group B). |
| 240 | 2952412 | Islet cell antibodies and/or DR3, DR4 heterozygosity were most common in the 70 patients diagnosed below the age of 40 years but were also found in older patients. |
| 241 | 2952412 | Fifty-six had islet cell antibodies and/or were heterozygous for HLA DR3 and DR4 (Group A) whereas 44 had neither of these markers (Group B). |
| 242 | 2952412 | Islet cell antibodies and/or DR3, DR4 heterozygosity were most common in the 70 patients diagnosed below the age of 40 years but were also found in older patients. |
| 243 | 2979618 | DR3 and DR4 have been the most positive and DR2 the most negative. |
| 244 | 2979618 | In 952 Caucasian proband patients reported here, only 57 or 6% had no DR3 or DR4 alleles. |
| 245 | 2979618 | When these 57 patients were compared to 249 Caucasian controls similarly lacking DR3 and DR4 antigens, there were excesses of DR1 (P = 0.13) and DRW8 (P = 0.01) and deficiencies of DR2 (P = 0.03) and DR5 (P = 0.03) in the patient group. |
| 246 | 2979618 | Only four DR-homozygous patients involving alleles other than DR3 and DR4 were found by genotyping, and all were DR1 homozygotes. |
| 247 | 2979618 | We conclude that DR1 is an additional risk DR allele for IDD to that of DR3 and DR4, and DR5 an additional protective DR allele to that of DR2. |
| 248 | 2979618 | DR3 and DR4 have been the most positive and DR2 the most negative. |
| 249 | 2979618 | In 952 Caucasian proband patients reported here, only 57 or 6% had no DR3 or DR4 alleles. |
| 250 | 2979618 | When these 57 patients were compared to 249 Caucasian controls similarly lacking DR3 and DR4 antigens, there were excesses of DR1 (P = 0.13) and DRW8 (P = 0.01) and deficiencies of DR2 (P = 0.03) and DR5 (P = 0.03) in the patient group. |
| 251 | 2979618 | Only four DR-homozygous patients involving alleles other than DR3 and DR4 were found by genotyping, and all were DR1 homozygotes. |
| 252 | 2979618 | We conclude that DR1 is an additional risk DR allele for IDD to that of DR3 and DR4, and DR5 an additional protective DR allele to that of DR2. |
| 253 | 2979618 | DR3 and DR4 have been the most positive and DR2 the most negative. |
| 254 | 2979618 | In 952 Caucasian proband patients reported here, only 57 or 6% had no DR3 or DR4 alleles. |
| 255 | 2979618 | When these 57 patients were compared to 249 Caucasian controls similarly lacking DR3 and DR4 antigens, there were excesses of DR1 (P = 0.13) and DRW8 (P = 0.01) and deficiencies of DR2 (P = 0.03) and DR5 (P = 0.03) in the patient group. |
| 256 | 2979618 | Only four DR-homozygous patients involving alleles other than DR3 and DR4 were found by genotyping, and all were DR1 homozygotes. |
| 257 | 2979618 | We conclude that DR1 is an additional risk DR allele for IDD to that of DR3 and DR4, and DR5 an additional protective DR allele to that of DR2. |
| 258 | 2979618 | DR3 and DR4 have been the most positive and DR2 the most negative. |
| 259 | 2979618 | In 952 Caucasian proband patients reported here, only 57 or 6% had no DR3 or DR4 alleles. |
| 260 | 2979618 | When these 57 patients were compared to 249 Caucasian controls similarly lacking DR3 and DR4 antigens, there were excesses of DR1 (P = 0.13) and DRW8 (P = 0.01) and deficiencies of DR2 (P = 0.03) and DR5 (P = 0.03) in the patient group. |
| 261 | 2979618 | Only four DR-homozygous patients involving alleles other than DR3 and DR4 were found by genotyping, and all were DR1 homozygotes. |
| 262 | 2979618 | We conclude that DR1 is an additional risk DR allele for IDD to that of DR3 and DR4, and DR5 an additional protective DR allele to that of DR2. |
| 263 | 2979618 | DR3 and DR4 have been the most positive and DR2 the most negative. |
| 264 | 2979618 | In 952 Caucasian proband patients reported here, only 57 or 6% had no DR3 or DR4 alleles. |
| 265 | 2979618 | When these 57 patients were compared to 249 Caucasian controls similarly lacking DR3 and DR4 antigens, there were excesses of DR1 (P = 0.13) and DRW8 (P = 0.01) and deficiencies of DR2 (P = 0.03) and DR5 (P = 0.03) in the patient group. |
| 266 | 2979618 | Only four DR-homozygous patients involving alleles other than DR3 and DR4 were found by genotyping, and all were DR1 homozygotes. |
| 267 | 2979618 | We conclude that DR1 is an additional risk DR allele for IDD to that of DR3 and DR4, and DR5 an additional protective DR allele to that of DR2. |
| 268 | 2987920 | (iii) A DR Taq I 14.5-kilobase-pair fragment was found to be strongly associated with DQR4, mainly in DR3/DR4 heterozygous patients (P = 5 X 10(-4). |
| 269 | 2994251 | Furthermore, for the mumps antigen the DR3- and DR4-determinants which are associated with Type 1 diabetes, seemed to have a different regulatory function on the T lymphocyte response in that an increased frequency of low responders was found among DR3 positive individuals and an increased frequency of high responders among DR4 positives. |
| 270 | 2995183 | The results suggest that elements on the DR3 and DR4 molecules may control T-lymphocyte responses to mumps and Coxsackie B4 viruses. |
| 271 | 2999795 | This restriction fragment pattern was found for several haplotypes associated with the DQw3 specificity, including some haplotypes positive for the HLA-DR specificities DR4, DR5, DRw8, and DRw12. |
| 272 | 3014039 | More than 90% of DR4+ IDDM patients express one of these alleles, DQ3.2; restriction enzyme mapping indicates that the presence of this allele also accounts for the genomic fragment patterns previously reported in IDDM. |
| 273 | 3014346 | Certain class II determinants of the human histocompatibility locus antigens (HLA) have been implicated in the aetiology of several autoimmune diseases, including rheumatoid arthritis (RA) and insulin-dependent diabetes mellitus (IDDM). |
| 274 | 3014346 | When the HLA-DR system was defined, RA patients were found to have an increased frequency of DR4 and IDDM patients an increased incidence of both DR4 and DR3 compared with controls. |
| 275 | 3057885 | From 11 studies, a total of 1,792 Caucasian probands with insulin-dependent diabetes mellitus (IDDM) are analyzed. |
| 276 | 3057885 | Removal of DR3 and DR4 reveals an overall protective effect of DR2, predisposing effects of DR1 and DRw8, and a slight protective effect of DR5 and a predisposing effect of DRw6. |
| 277 | 3057885 | The non-DR3, non-DR4 antigens are not independently associated with DR3 and DR4; the largest effect is a deficiency of DR2, followed by excesses of DR1, DRw8, and DRw6, in DR4 individuals, as compared with DR3 individuals. |
| 278 | 3057885 | HLA-B locus distributions on patient haplotypes indicate that only subsets of both DR3 and DR4 are predisposing. |
| 279 | 3057885 | At a minimum, the distinguishing features of the DR3-associated and DR4-associated predisposition remain to be identified at the molecular level. |
| 280 | 3057885 | Risk estimates subdivided by the DR type of the proband are also calculated, the highest being 19.2% for sibs sharing two haplotypes with a DR3/DR4 proband. |
| 281 | 3057885 | From 11 studies, a total of 1,792 Caucasian probands with insulin-dependent diabetes mellitus (IDDM) are analyzed. |
| 282 | 3057885 | Removal of DR3 and DR4 reveals an overall protective effect of DR2, predisposing effects of DR1 and DRw8, and a slight protective effect of DR5 and a predisposing effect of DRw6. |
| 283 | 3057885 | The non-DR3, non-DR4 antigens are not independently associated with DR3 and DR4; the largest effect is a deficiency of DR2, followed by excesses of DR1, DRw8, and DRw6, in DR4 individuals, as compared with DR3 individuals. |
| 284 | 3057885 | HLA-B locus distributions on patient haplotypes indicate that only subsets of both DR3 and DR4 are predisposing. |
| 285 | 3057885 | At a minimum, the distinguishing features of the DR3-associated and DR4-associated predisposition remain to be identified at the molecular level. |
| 286 | 3057885 | Risk estimates subdivided by the DR type of the proband are also calculated, the highest being 19.2% for sibs sharing two haplotypes with a DR3/DR4 proband. |
| 287 | 3057885 | From 11 studies, a total of 1,792 Caucasian probands with insulin-dependent diabetes mellitus (IDDM) are analyzed. |
| 288 | 3057885 | Removal of DR3 and DR4 reveals an overall protective effect of DR2, predisposing effects of DR1 and DRw8, and a slight protective effect of DR5 and a predisposing effect of DRw6. |
| 289 | 3057885 | The non-DR3, non-DR4 antigens are not independently associated with DR3 and DR4; the largest effect is a deficiency of DR2, followed by excesses of DR1, DRw8, and DRw6, in DR4 individuals, as compared with DR3 individuals. |
| 290 | 3057885 | HLA-B locus distributions on patient haplotypes indicate that only subsets of both DR3 and DR4 are predisposing. |
| 291 | 3057885 | At a minimum, the distinguishing features of the DR3-associated and DR4-associated predisposition remain to be identified at the molecular level. |
| 292 | 3057885 | Risk estimates subdivided by the DR type of the proband are also calculated, the highest being 19.2% for sibs sharing two haplotypes with a DR3/DR4 proband. |
| 293 | 3057885 | From 11 studies, a total of 1,792 Caucasian probands with insulin-dependent diabetes mellitus (IDDM) are analyzed. |
| 294 | 3057885 | Removal of DR3 and DR4 reveals an overall protective effect of DR2, predisposing effects of DR1 and DRw8, and a slight protective effect of DR5 and a predisposing effect of DRw6. |
| 295 | 3057885 | The non-DR3, non-DR4 antigens are not independently associated with DR3 and DR4; the largest effect is a deficiency of DR2, followed by excesses of DR1, DRw8, and DRw6, in DR4 individuals, as compared with DR3 individuals. |
| 296 | 3057885 | HLA-B locus distributions on patient haplotypes indicate that only subsets of both DR3 and DR4 are predisposing. |
| 297 | 3057885 | At a minimum, the distinguishing features of the DR3-associated and DR4-associated predisposition remain to be identified at the molecular level. |
| 298 | 3057885 | Risk estimates subdivided by the DR type of the proband are also calculated, the highest being 19.2% for sibs sharing two haplotypes with a DR3/DR4 proband. |
| 299 | 3057885 | From 11 studies, a total of 1,792 Caucasian probands with insulin-dependent diabetes mellitus (IDDM) are analyzed. |
| 300 | 3057885 | Removal of DR3 and DR4 reveals an overall protective effect of DR2, predisposing effects of DR1 and DRw8, and a slight protective effect of DR5 and a predisposing effect of DRw6. |
| 301 | 3057885 | The non-DR3, non-DR4 antigens are not independently associated with DR3 and DR4; the largest effect is a deficiency of DR2, followed by excesses of DR1, DRw8, and DRw6, in DR4 individuals, as compared with DR3 individuals. |
| 302 | 3057885 | HLA-B locus distributions on patient haplotypes indicate that only subsets of both DR3 and DR4 are predisposing. |
| 303 | 3057885 | At a minimum, the distinguishing features of the DR3-associated and DR4-associated predisposition remain to be identified at the molecular level. |
| 304 | 3057885 | Risk estimates subdivided by the DR type of the proband are also calculated, the highest being 19.2% for sibs sharing two haplotypes with a DR3/DR4 proband. |
| 305 | 3071483 | Analysis of HLA haplotypes within families illustrated the high frequency of DR3 and DR4 alleles with preferential transmission from parent to both affected and unaffected offspring. |
| 306 | 3075129 | These results support the heterogeneity of the autoantibodies: ICA are related closely to diabetes, decline in frequency with the duration of the disease and show association with DR3 or DR4 and the number of HLA haplotypes shared with the proband; EPA are sex related, independent of the duration of diabetes, non-HLA linked, and clustered in families with parent-offspring overtransmission, reflecting an overlapping autoimmune background. |
| 307 | 3082114 | Moreover, a strong genetic association with HL-A DR3 and DR4 identifies a genetic background compatible with autoimmune phenomena. |
| 308 | 3125628 | Thirty-one Ethiopian insulin-dependent (or type I) diabetes mellitus (IDDM) patients and thirty-three healthy controls from the same ethnic background were typed for HLA-A, B, C, DR and DQ specificities. |
| 309 | 3125628 | The frequencies of both DR3 and DR4 were significantly increased among IDDM patients (resp. p = 0.02, p = 0.01), confirming results in other populations. |
| 310 | 3125628 | Although this latter difference does not retain statistical significance after correction for the number of comparisons made, these findings may support previous results suggesting the existence of IDDM susceptibility genes associated with DR3 and DR4 and of IDDM resistance genes associated with DQ antigens. |
| 311 | 3125628 | Thirty-one Ethiopian insulin-dependent (or type I) diabetes mellitus (IDDM) patients and thirty-three healthy controls from the same ethnic background were typed for HLA-A, B, C, DR and DQ specificities. |
| 312 | 3125628 | The frequencies of both DR3 and DR4 were significantly increased among IDDM patients (resp. p = 0.02, p = 0.01), confirming results in other populations. |
| 313 | 3125628 | Although this latter difference does not retain statistical significance after correction for the number of comparisons made, these findings may support previous results suggesting the existence of IDDM susceptibility genes associated with DR3 and DR4 and of IDDM resistance genes associated with DQ antigens. |
| 314 | 3139557 | In the genetically homogeneous Danish population, 27 HLA-DR3,4 heterozygous patients with insulin-dependent diabetes mellitus (IDDM) and 19 DR3,4 heterozygous controls without family history of IDDM were investigated for HLA-region markers and Gm and Km immunoglobulin allotypes. |
| 315 | 3139557 | Previously reported family studies suggest that these alleles are part of the following haplotype: B15, BFS, C4A3, C4B3, DR4, Dw4, DQw8, and these factors were found together in ten of the patients versus one of the controls (P = 0.01). |
| 316 | 3139557 | In addition to the susceptibility factor DQw8, the study suggests the existence of susceptibility genes for IDDM near the complement C4 genes on DR4-carrying haplotypes. |
| 317 | 3139557 | In the genetically homogeneous Danish population, 27 HLA-DR3,4 heterozygous patients with insulin-dependent diabetes mellitus (IDDM) and 19 DR3,4 heterozygous controls without family history of IDDM were investigated for HLA-region markers and Gm and Km immunoglobulin allotypes. |
| 318 | 3139557 | Previously reported family studies suggest that these alleles are part of the following haplotype: B15, BFS, C4A3, C4B3, DR4, Dw4, DQw8, and these factors were found together in ten of the patients versus one of the controls (P = 0.01). |
| 319 | 3139557 | In addition to the susceptibility factor DQw8, the study suggests the existence of susceptibility genes for IDDM near the complement C4 genes on DR4-carrying haplotypes. |
| 320 | 3149191 | Associations of insulin dependent diabetes mellitus exist with the HLA-DR antigens DR3 and DR4 in both British Caucasoid and Dravidian subjects. |
| 321 | 3163697 | Compared with the normal subjects, HLA-A28 was more frequent in the patients with hypoparathyroidism (31%; P less than 0.001, corrected P less than 0.04), adrenocortical failure (27%; P less than 0.01), insulin-dependent diabetes mellitus (IDDM; 66%; P less than 0.01), keratopathy (53%; P less than 0.001, corrected P less than 0.04), and alopecia (40%; P less than 0.001, corrected P less than 0.04), but not in the patients with ovarian failure (9%; P = NS). |
| 322 | 3163697 | No association was found with any single DR antigen, but of 4 DR-typed IDDM patients, 3 were DR3 or DR4 positive (P = NS). |
| 323 | 3217930 | Two complotypes, BfSC4A3B3 and SC4A0B1, were significantly more common (P less than 0.05) in the diabetic haplotypes, and these were in most cases found in haplotypic combinations with HLA-B15,Dw4,DR4 and HLA-B8,Dw3,DR3 genes, respectively. |
| 324 | 3217930 | "B15,BfS,C4A3B3,Dw4,DR4" and "B8,Bfs,C4A0B1,Dw3,DR3" are inherited as haplotypes. |
| 325 | 3217930 | Two complotypes, BfSC4A3B3 and SC4A0B1, were significantly more common (P less than 0.05) in the diabetic haplotypes, and these were in most cases found in haplotypic combinations with HLA-B15,Dw4,DR4 and HLA-B8,Dw3,DR3 genes, respectively. |
| 326 | 3217930 | "B15,BfS,C4A3B3,Dw4,DR4" and "B8,Bfs,C4A0B1,Dw3,DR3" are inherited as haplotypes. |
| 327 | 3238312 | In order to define genetic, immunological and metabolic risk factors and markers associated with diabetic neuropathy (DN) 47 insulin-dependent diabetic patients with neuropathy were compared to 30 age-matched insulin-dependent diabetes mellitus (IDDM) patients without neuropathy. |
| 328 | 3238312 | The frequency of HLA-antigens DR3, DR4, DR3/DR4, B8, and B15 were increased and those of DR2 and B7 decreased in the diabetic patients. |
| 329 | 3238312 | However, patients who were HLA-DR3/DR4 heterozygotes and had diabetic neuropathy responded to insulin antigens more often by proliferation than DR3/DR4 positive patients without diabetic neuropathy. |
| 330 | 3238312 | Patients with DR3/DR4 heterozygocity and failing to respond to insulin antigens by proliferation seem to be less prone to develop diabetic neuropathy. |
| 331 | 3238312 | In order to define genetic, immunological and metabolic risk factors and markers associated with diabetic neuropathy (DN) 47 insulin-dependent diabetic patients with neuropathy were compared to 30 age-matched insulin-dependent diabetes mellitus (IDDM) patients without neuropathy. |
| 332 | 3238312 | The frequency of HLA-antigens DR3, DR4, DR3/DR4, B8, and B15 were increased and those of DR2 and B7 decreased in the diabetic patients. |
| 333 | 3238312 | However, patients who were HLA-DR3/DR4 heterozygotes and had diabetic neuropathy responded to insulin antigens more often by proliferation than DR3/DR4 positive patients without diabetic neuropathy. |
| 334 | 3238312 | Patients with DR3/DR4 heterozygocity and failing to respond to insulin antigens by proliferation seem to be less prone to develop diabetic neuropathy. |
| 335 | 3238312 | In order to define genetic, immunological and metabolic risk factors and markers associated with diabetic neuropathy (DN) 47 insulin-dependent diabetic patients with neuropathy were compared to 30 age-matched insulin-dependent diabetes mellitus (IDDM) patients without neuropathy. |
| 336 | 3238312 | The frequency of HLA-antigens DR3, DR4, DR3/DR4, B8, and B15 were increased and those of DR2 and B7 decreased in the diabetic patients. |
| 337 | 3238312 | However, patients who were HLA-DR3/DR4 heterozygotes and had diabetic neuropathy responded to insulin antigens more often by proliferation than DR3/DR4 positive patients without diabetic neuropathy. |
| 338 | 3238312 | Patients with DR3/DR4 heterozygocity and failing to respond to insulin antigens by proliferation seem to be less prone to develop diabetic neuropathy. |
| 339 | 3264044 | A hypothesis about the evolution of insulin-dependent diabetes mellitus (IDDM)-susceptibility alleles is proposed. |
| 340 | 3264044 | IDDM is known to be associated with two HLA-DR alleles, DR3 and DR4. |
| 341 | 3264044 | However, in general, DR4 is associated with IDDM only in populations with white ancestry with high rates of IDDM. |
| 342 | 3264044 | The frequency of IDDM in American blacks relative to that in American whites (20% to 30%) approximates the frequency of the American black gene pool that is white-derived (also 20% to 30%), and DR4 is associated with IDDM in American blacks but not in African blacks. |
| 343 | 3264044 | A hypothesis about the evolution of insulin-dependent diabetes mellitus (IDDM)-susceptibility alleles is proposed. |
| 344 | 3264044 | IDDM is known to be associated with two HLA-DR alleles, DR3 and DR4. |
| 345 | 3264044 | However, in general, DR4 is associated with IDDM only in populations with white ancestry with high rates of IDDM. |
| 346 | 3264044 | The frequency of IDDM in American blacks relative to that in American whites (20% to 30%) approximates the frequency of the American black gene pool that is white-derived (also 20% to 30%), and DR4 is associated with IDDM in American blacks but not in African blacks. |
| 347 | 3264044 | A hypothesis about the evolution of insulin-dependent diabetes mellitus (IDDM)-susceptibility alleles is proposed. |
| 348 | 3264044 | IDDM is known to be associated with two HLA-DR alleles, DR3 and DR4. |
| 349 | 3264044 | However, in general, DR4 is associated with IDDM only in populations with white ancestry with high rates of IDDM. |
| 350 | 3264044 | The frequency of IDDM in American blacks relative to that in American whites (20% to 30%) approximates the frequency of the American black gene pool that is white-derived (also 20% to 30%), and DR4 is associated with IDDM in American blacks but not in African blacks. |
| 351 | 3275559 | Islet cell antibodies (ICAs), thyrogastric antibodies, and HLA-DR antigens were determined in 204 patients with type II (non-insulin-dependent) diabetes controlled with diet and/or oral hypoglycemic agents (NIR) and in 108 age-matched patients who required insulin to control their hyperglycemia (IR). beta-Cell function measured as C-peptide response to glucagon was evaluated in relation to the presence of ICAs and HLA-DR antigens. |
| 352 | 3275559 | Neither the presence of ICA alone nor DR3/DR4 alone was associated with a significant impairment of beta-cell function. |
| 353 | 3275559 | However, when both ICA and DR3/DR4 were present in a diabetic individual, beta-cell function was markedly impaired (P less than .001), suggesting that both genetic and autoimmune factors are necessary to facilitate the process leading to beta-cell destruction of the patients. |
| 354 | 3275559 | Islet cell antibodies (ICAs), thyrogastric antibodies, and HLA-DR antigens were determined in 204 patients with type II (non-insulin-dependent) diabetes controlled with diet and/or oral hypoglycemic agents (NIR) and in 108 age-matched patients who required insulin to control their hyperglycemia (IR). beta-Cell function measured as C-peptide response to glucagon was evaluated in relation to the presence of ICAs and HLA-DR antigens. |
| 355 | 3275559 | Neither the presence of ICA alone nor DR3/DR4 alone was associated with a significant impairment of beta-cell function. |
| 356 | 3275559 | However, when both ICA and DR3/DR4 were present in a diabetic individual, beta-cell function was markedly impaired (P less than .001), suggesting that both genetic and autoimmune factors are necessary to facilitate the process leading to beta-cell destruction of the patients. |
| 357 | 3291550 | The Wolfram, or DIDMOAD, syndrome is a rare congenital disease that is associated with diabetes insipidus, insulin dependent diabetes mellitus of an early onset, bilateral optic atrophy and deafness. |
| 358 | 3291550 | On the basis of some of the clinical features it was also possible to further distinguish between the DIDMOAD syndrome and the classical insulin dependent diabetes mellitus. |
| 359 | 3291550 | The differences encountered between classical and DIDMOAD insulin dependent diabetes mellitus--the presence/absence of HLA linkage, HLA-DR2, -DR3 and -DR4 associations, islet cell or antinuclear antibodies, the tendency to ketosis and diabetic retinopathy--indicate that their etiopathogenies are triggered by distinct mechanisms. |
| 360 | 3301240 | Genetic studies indicate that the IDDM susceptibility genes in the HLA region are closely linked to the DR3 and DR4 specificities; however, these specificities do not define the actual susceptibility genes. |
| 361 | 3301240 | For example, the DX alpha, 2.1-kb Taql polymorphism shows a stronger correlation with IDDM than DR3. |
| 362 | 3307406 | Insulin-dependent diabetes mellitus (IDDM) is caused by the destruction of the beta cells of the pancreas. |
| 363 | 3307406 | The risk is greatest for those with both DR3 and DR4. |
| 364 | 3315368 | Diminished complications in a non DR3 DR4 family with insulin-dependent diabetes. |
| 365 | 3326380 | The analysis of variance of urinary C-peptide values on the basis of the presence or absence of DR3 and DR4 antigens revealed that the DR3-positive patients had reduced excretion (15.2 +/- 9.2 SD micrograms/24h) with respect to the others (22.7 +/- 15.5 SD micrograms/24h) (F = 6.35; p less than 0.05). |
| 366 | 3365534 | HLA typing revealed the presence of HLA A2, A9, B8, B27, DR3 and DR4 antigens. |
| 367 | 3372263 | To examine the nature of HLA-linked genetic susceptibility to insulin-dependent diabetes mellitus (IDDM), we compared HLA class II gene sequences from IDDM patients and control individuals. |
| 368 | 3372263 | These libraries represent the HLA haplotypes (DR3, DR4) most frequently associated with IDDM, as well as one haplotype found less often. |
| 369 | 3400091 | From the study of HLA, A, B, C, DR, Bf and C4A, C4B alleles in 287 insulin-dependent diabetes mellitus patients and 108 controls, comparisons were made between 424 diabetic and 216 normal extended haplotypes. |
| 370 | 3400091 | In the "cis" situation (haplotype), the highest relative risks (RR) for IDDM were borne by multiloci allelic associations, mainly DR/complement alleles, rather than by DR3 or DR4 considered alone. |
| 371 | 3400091 | Susceptibility was strongly associated with two extended haplotypes (Aw30, Cw5, B18, C4BQ0, C4A3, BfF1, DR3 and A2, Cw3, B15, C4Bx, C4A3, BfS, DR4) or their smaller segments. |
| 372 | 3400091 | In the "trans" situation (opposite haplotype) the large excess of DR3/DR4 heterozygotes was not the only distortion observed. |
| 373 | 3400091 | Homozygotes for DR3 or DR4 were not increased, and other homozygotes were decreased compared to controls. |
| 374 | 3400091 | From the study of HLA, A, B, C, DR, Bf and C4A, C4B alleles in 287 insulin-dependent diabetes mellitus patients and 108 controls, comparisons were made between 424 diabetic and 216 normal extended haplotypes. |
| 375 | 3400091 | In the "cis" situation (haplotype), the highest relative risks (RR) for IDDM were borne by multiloci allelic associations, mainly DR/complement alleles, rather than by DR3 or DR4 considered alone. |
| 376 | 3400091 | Susceptibility was strongly associated with two extended haplotypes (Aw30, Cw5, B18, C4BQ0, C4A3, BfF1, DR3 and A2, Cw3, B15, C4Bx, C4A3, BfS, DR4) or their smaller segments. |
| 377 | 3400091 | In the "trans" situation (opposite haplotype) the large excess of DR3/DR4 heterozygotes was not the only distortion observed. |
| 378 | 3400091 | Homozygotes for DR3 or DR4 were not increased, and other homozygotes were decreased compared to controls. |
| 379 | 3400091 | From the study of HLA, A, B, C, DR, Bf and C4A, C4B alleles in 287 insulin-dependent diabetes mellitus patients and 108 controls, comparisons were made between 424 diabetic and 216 normal extended haplotypes. |
| 380 | 3400091 | In the "cis" situation (haplotype), the highest relative risks (RR) for IDDM were borne by multiloci allelic associations, mainly DR/complement alleles, rather than by DR3 or DR4 considered alone. |
| 381 | 3400091 | Susceptibility was strongly associated with two extended haplotypes (Aw30, Cw5, B18, C4BQ0, C4A3, BfF1, DR3 and A2, Cw3, B15, C4Bx, C4A3, BfS, DR4) or their smaller segments. |
| 382 | 3400091 | In the "trans" situation (opposite haplotype) the large excess of DR3/DR4 heterozygotes was not the only distortion observed. |
| 383 | 3400091 | Homozygotes for DR3 or DR4 were not increased, and other homozygotes were decreased compared to controls. |
| 384 | 3400091 | From the study of HLA, A, B, C, DR, Bf and C4A, C4B alleles in 287 insulin-dependent diabetes mellitus patients and 108 controls, comparisons were made between 424 diabetic and 216 normal extended haplotypes. |
| 385 | 3400091 | In the "cis" situation (haplotype), the highest relative risks (RR) for IDDM were borne by multiloci allelic associations, mainly DR/complement alleles, rather than by DR3 or DR4 considered alone. |
| 386 | 3400091 | Susceptibility was strongly associated with two extended haplotypes (Aw30, Cw5, B18, C4BQ0, C4A3, BfF1, DR3 and A2, Cw3, B15, C4Bx, C4A3, BfS, DR4) or their smaller segments. |
| 387 | 3400091 | In the "trans" situation (opposite haplotype) the large excess of DR3/DR4 heterozygotes was not the only distortion observed. |
| 388 | 3400091 | Homozygotes for DR3 or DR4 were not increased, and other homozygotes were decreased compared to controls. |
| 389 | 3456943 | Because the strong HLA associations with type I diabetes in American Blacks are the same as in Caucasians (i.e., increased DR3 and DR4 and decreased DR2), the genetic contribution (i.e., the lack of an association with DR4) to susceptibility to type I diabetes in most Nigerian Blacks may be different from that in most Caucasians and American Blacks. |
| 390 | 3462067 | The data obtained suggest that the association with DR3 and DR4 is secondary to that with DQ specificities in linkage disequilibrium with DR3 and DR4. |
| 391 | 3471665 | DR4 and DR3 are in strongest linkage disequilibrium with IDDM susceptibility genes, and DR1 demonstrates a lesser degree of positive disequilibrium. |
| 392 | 3471665 | DR3/DR4 heterozygotes have the highest risk. |
| 393 | 3471665 | The DR1 increase occurs almost exclusively in DR4/DR1 heterozygotes, suggesting that DR1 may be in disequilibrium with the same susceptibility gene as DR3. |
| 394 | 3471665 | GLO-2 is increased in diabetic haplotypes carrying DR4, DR3 or DR1. |
| 395 | 3471665 | DR4 and DR3 are in strongest linkage disequilibrium with IDDM susceptibility genes, and DR1 demonstrates a lesser degree of positive disequilibrium. |
| 396 | 3471665 | DR3/DR4 heterozygotes have the highest risk. |
| 397 | 3471665 | The DR1 increase occurs almost exclusively in DR4/DR1 heterozygotes, suggesting that DR1 may be in disequilibrium with the same susceptibility gene as DR3. |
| 398 | 3471665 | GLO-2 is increased in diabetic haplotypes carrying DR4, DR3 or DR1. |
| 399 | 3471665 | DR4 and DR3 are in strongest linkage disequilibrium with IDDM susceptibility genes, and DR1 demonstrates a lesser degree of positive disequilibrium. |
| 400 | 3471665 | DR3/DR4 heterozygotes have the highest risk. |
| 401 | 3471665 | The DR1 increase occurs almost exclusively in DR4/DR1 heterozygotes, suggesting that DR1 may be in disequilibrium with the same susceptibility gene as DR3. |
| 402 | 3471665 | GLO-2 is increased in diabetic haplotypes carrying DR4, DR3 or DR1. |
| 403 | 3471665 | DR4 and DR3 are in strongest linkage disequilibrium with IDDM susceptibility genes, and DR1 demonstrates a lesser degree of positive disequilibrium. |
| 404 | 3471665 | DR3/DR4 heterozygotes have the highest risk. |
| 405 | 3471665 | The DR1 increase occurs almost exclusively in DR4/DR1 heterozygotes, suggesting that DR1 may be in disequilibrium with the same susceptibility gene as DR3. |
| 406 | 3471665 | GLO-2 is increased in diabetic haplotypes carrying DR4, DR3 or DR1. |
| 407 | 3484749 | The inherited susceptibility to autoimmune Addison's disease was found to be strongly associated with human leukocyte antigens (HLA)-DR3 and DR4 alleles. |
| 408 | 3484749 | These HLA-DR frequencies in patients with Addison's disease were similar to those for 723 patients with insulin-dependent diabetes (IDD). |
| 409 | 3484749 | Adrenocortical autoantibodies in 23 patients with IDD who did not have Addison's disease were equally frequent among those with DR4 and DR3 alleles. |
| 410 | 3484749 | The inherited susceptibility to autoimmune Addison's disease was found to be strongly associated with human leukocyte antigens (HLA)-DR3 and DR4 alleles. |
| 411 | 3484749 | These HLA-DR frequencies in patients with Addison's disease were similar to those for 723 patients with insulin-dependent diabetes (IDD). |
| 412 | 3484749 | Adrenocortical autoantibodies in 23 patients with IDD who did not have Addison's disease were equally frequent among those with DR4 and DR3 alleles. |
| 413 | 3485759 | In this series, however, HLA-DR3/DR4 heterozygotes were apparently at no greater risk for type I diabetes than DR3 or DR4 homozygotes. |
| 414 | 3485759 | The relative risk conferred by DR3/DR4 heterozygotes (6.48) was less than that for DR3 homozygosity (2.8), suggesting a recessive major histocompatibility complex-related susceptibility to type I diabetes. |
| 415 | 3485759 | In this series, however, HLA-DR3/DR4 heterozygotes were apparently at no greater risk for type I diabetes than DR3 or DR4 homozygotes. |
| 416 | 3485759 | The relative risk conferred by DR3/DR4 heterozygotes (6.48) was less than that for DR3 homozygosity (2.8), suggesting a recessive major histocompatibility complex-related susceptibility to type I diabetes. |
| 417 | 3488933 | There were no significant differences in the gene frequencies of the insulin-dependent diabetes mellitus (IDDM)-associated alleles, DR3 and DR4, and whereas the DR3/4 heterozygotes were as frequent among simplex probands as among the first affected of multiplex sibships, subsequently affected sibs displayed lower frequencies of this genotype in this as well as in previously reported samples, indicating that the excessive risk associated with DR3/4 heterozygosity depends on the order of affection and thus on environmental factors. |
| 418 | 3489237 | Insulin-dependent diabetes mellitus (IDDM) susceptibility determinants are known to be associated with both HLA-DR3 and -DR4. |
| 419 | 3489237 | The proportion of nondiabetic parents who transmitted DR4 to diabetic offspring (22%) was not significantly different from the gene frequency of DR4 in the nondiabetic population (16%), but it was significantly lower (P less than 0.05) than the gene frequency in the overall IDDM population. |
| 420 | 3489237 | These proportions suggest that inheritance of the DR4-associated IDDM susceptibility determinant is not recessive, because in recessive inheritance expression of a trait depends on each parent contributing a susceptibility determinant. |
| 421 | 3489237 | The transmission of predominantly DR4 from affected parents to affected offspring suggests that susceptibility to IDDM is inherited primarily via a single dose of a potent determinant associated with DR4, as in dominant inheritance. |
| 422 | 3489237 | Numerous population data indicate that the DR3DR4 genotype carries a higher relative risk for IDDM than any other genotype, which suggests synergism between the DR3- and DR4-associated determinants. |
| 423 | 3489237 | Insulin-dependent diabetes mellitus (IDDM) susceptibility determinants are known to be associated with both HLA-DR3 and -DR4. |
| 424 | 3489237 | The proportion of nondiabetic parents who transmitted DR4 to diabetic offspring (22%) was not significantly different from the gene frequency of DR4 in the nondiabetic population (16%), but it was significantly lower (P less than 0.05) than the gene frequency in the overall IDDM population. |
| 425 | 3489237 | These proportions suggest that inheritance of the DR4-associated IDDM susceptibility determinant is not recessive, because in recessive inheritance expression of a trait depends on each parent contributing a susceptibility determinant. |
| 426 | 3489237 | The transmission of predominantly DR4 from affected parents to affected offspring suggests that susceptibility to IDDM is inherited primarily via a single dose of a potent determinant associated with DR4, as in dominant inheritance. |
| 427 | 3489237 | Numerous population data indicate that the DR3DR4 genotype carries a higher relative risk for IDDM than any other genotype, which suggests synergism between the DR3- and DR4-associated determinants. |
| 428 | 3489237 | Insulin-dependent diabetes mellitus (IDDM) susceptibility determinants are known to be associated with both HLA-DR3 and -DR4. |
| 429 | 3489237 | The proportion of nondiabetic parents who transmitted DR4 to diabetic offspring (22%) was not significantly different from the gene frequency of DR4 in the nondiabetic population (16%), but it was significantly lower (P less than 0.05) than the gene frequency in the overall IDDM population. |
| 430 | 3489237 | These proportions suggest that inheritance of the DR4-associated IDDM susceptibility determinant is not recessive, because in recessive inheritance expression of a trait depends on each parent contributing a susceptibility determinant. |
| 431 | 3489237 | The transmission of predominantly DR4 from affected parents to affected offspring suggests that susceptibility to IDDM is inherited primarily via a single dose of a potent determinant associated with DR4, as in dominant inheritance. |
| 432 | 3489237 | Numerous population data indicate that the DR3DR4 genotype carries a higher relative risk for IDDM than any other genotype, which suggests synergism between the DR3- and DR4-associated determinants. |
| 433 | 3489237 | Insulin-dependent diabetes mellitus (IDDM) susceptibility determinants are known to be associated with both HLA-DR3 and -DR4. |
| 434 | 3489237 | The proportion of nondiabetic parents who transmitted DR4 to diabetic offspring (22%) was not significantly different from the gene frequency of DR4 in the nondiabetic population (16%), but it was significantly lower (P less than 0.05) than the gene frequency in the overall IDDM population. |
| 435 | 3489237 | These proportions suggest that inheritance of the DR4-associated IDDM susceptibility determinant is not recessive, because in recessive inheritance expression of a trait depends on each parent contributing a susceptibility determinant. |
| 436 | 3489237 | The transmission of predominantly DR4 from affected parents to affected offspring suggests that susceptibility to IDDM is inherited primarily via a single dose of a potent determinant associated with DR4, as in dominant inheritance. |
| 437 | 3489237 | Numerous population data indicate that the DR3DR4 genotype carries a higher relative risk for IDDM than any other genotype, which suggests synergism between the DR3- and DR4-associated determinants. |
| 438 | 3489237 | Insulin-dependent diabetes mellitus (IDDM) susceptibility determinants are known to be associated with both HLA-DR3 and -DR4. |
| 439 | 3489237 | The proportion of nondiabetic parents who transmitted DR4 to diabetic offspring (22%) was not significantly different from the gene frequency of DR4 in the nondiabetic population (16%), but it was significantly lower (P less than 0.05) than the gene frequency in the overall IDDM population. |
| 440 | 3489237 | These proportions suggest that inheritance of the DR4-associated IDDM susceptibility determinant is not recessive, because in recessive inheritance expression of a trait depends on each parent contributing a susceptibility determinant. |
| 441 | 3489237 | The transmission of predominantly DR4 from affected parents to affected offspring suggests that susceptibility to IDDM is inherited primarily via a single dose of a potent determinant associated with DR4, as in dominant inheritance. |
| 442 | 3489237 | Numerous population data indicate that the DR3DR4 genotype carries a higher relative risk for IDDM than any other genotype, which suggests synergism between the DR3- and DR4-associated determinants. |
| 443 | 3491769 | The HLA association with insulin-dependent diabetes mellitus is highest among individuals heterozygous for DR3 and DR4. |
| 444 | 3491769 | These studies demonstrated hybrid molecular dimers corresponding to products of HLA-DQ genes linked to DR3 and DR4, i.e., the DQw2 and DQw3 genes, respectively. |
| 445 | 3491769 | The formation of such DQ alpha (DQw2)-Dq beta (DQw3) dimers potentially contributes a direct molecular mechanism for HLA-associated contributions to disease in DR3/DR4 heterozygotes. |
| 446 | 3491769 | The HLA association with insulin-dependent diabetes mellitus is highest among individuals heterozygous for DR3 and DR4. |
| 447 | 3491769 | These studies demonstrated hybrid molecular dimers corresponding to products of HLA-DQ genes linked to DR3 and DR4, i.e., the DQw2 and DQw3 genes, respectively. |
| 448 | 3491769 | The formation of such DQ alpha (DQw2)-Dq beta (DQw3) dimers potentially contributes a direct molecular mechanism for HLA-associated contributions to disease in DR3/DR4 heterozygotes. |
| 449 | 3491769 | The HLA association with insulin-dependent diabetes mellitus is highest among individuals heterozygous for DR3 and DR4. |
| 450 | 3491769 | These studies demonstrated hybrid molecular dimers corresponding to products of HLA-DQ genes linked to DR3 and DR4, i.e., the DQw2 and DQw3 genes, respectively. |
| 451 | 3491769 | The formation of such DQ alpha (DQw2)-Dq beta (DQw3) dimers potentially contributes a direct molecular mechanism for HLA-associated contributions to disease in DR3/DR4 heterozygotes. |
| 452 | 3495390 | We have reported an increased frequency of the rare B3 allotype of the fourth component of complement (C4B3) in insulin-dependent diabetics, especially in those with microangiopathy. |
| 453 | 3495390 | These results confirm an HLA-linked predisposition to microangiopathy, but do not determine whether the primary association is with C4B3, DR4 or another gene with which they are in linkage disequilibrium. |
| 454 | 3497749 | HLA typing of 100 Type 1 diabetic patients from the Rome area confirmed the strong association with DR3 and DR4 and the prevalence of DR3/4 heterozygotes. |
| 455 | 3531993 | The relative risks (RR) of the immunogenetic markers of insulin-dependent diabetes mellitus (IDDM) have been calculated in a population of 235 IDDM patients compared with a control population. |
| 456 | 3531993 | The highest relative risk was that of subjects heterozygous DR3/DR4 (RR = 47, P less than 0.001) which was still more increased in those who carry this combination associated with the RFLP cluster DQR4 (RR = 72). |
| 457 | 3531993 | The highest risks have been found in addition to DR3/DR4, for DR3 alone and particularly for the combination C4BQ0, DR3 (RR = 9, p less than 0.001) suggesting a role for this peculiar association in the familial penetrance. |
| 458 | 3531993 | In the group of haploidentical siblings, the combination DR3/DR4 and the associations C4BQ0, DR3 and BfF1, DR3 significantly increased the susceptibility for higher familial occurrence of the disease. |
| 459 | 3531993 | The relative risks (RR) of the immunogenetic markers of insulin-dependent diabetes mellitus (IDDM) have been calculated in a population of 235 IDDM patients compared with a control population. |
| 460 | 3531993 | The highest relative risk was that of subjects heterozygous DR3/DR4 (RR = 47, P less than 0.001) which was still more increased in those who carry this combination associated with the RFLP cluster DQR4 (RR = 72). |
| 461 | 3531993 | The highest risks have been found in addition to DR3/DR4, for DR3 alone and particularly for the combination C4BQ0, DR3 (RR = 9, p less than 0.001) suggesting a role for this peculiar association in the familial penetrance. |
| 462 | 3531993 | In the group of haploidentical siblings, the combination DR3/DR4 and the associations C4BQ0, DR3 and BfF1, DR3 significantly increased the susceptibility for higher familial occurrence of the disease. |
| 463 | 3531993 | The relative risks (RR) of the immunogenetic markers of insulin-dependent diabetes mellitus (IDDM) have been calculated in a population of 235 IDDM patients compared with a control population. |
| 464 | 3531993 | The highest relative risk was that of subjects heterozygous DR3/DR4 (RR = 47, P less than 0.001) which was still more increased in those who carry this combination associated with the RFLP cluster DQR4 (RR = 72). |
| 465 | 3531993 | The highest risks have been found in addition to DR3/DR4, for DR3 alone and particularly for the combination C4BQ0, DR3 (RR = 9, p less than 0.001) suggesting a role for this peculiar association in the familial penetrance. |
| 466 | 3531993 | In the group of haploidentical siblings, the combination DR3/DR4 and the associations C4BQ0, DR3 and BfF1, DR3 significantly increased the susceptibility for higher familial occurrence of the disease. |
| 467 | 3545954 | The Type 1 diabetic patients showed a typical HLA pattern, with increased frequencies of B15, DR3, DR4, B8/B15 and DR3/DR4 and decreased frequencies of B7 and DR2. |
| 468 | 3545954 | The Type 2 diabetic patients could be distinguished from blood donors by increased frequencies of Cw4, DR4, DR5 and DR3/DR4, and from Type 1 diabetic patients by increased frequencies of B7, DR2, DR5 and decreased frequency of A9, Bw22 and DR4. |
| 469 | 3545954 | Age at onset and body mass index were unrelated to HLA antigens, but the Type 2 diabetic patients with HLA-Cw4, DR5 and DR6 showed a strong family history for Type 2 diabetes. |
| 470 | 3545954 | Type 2 diabetic patients with HLA-B8, DR4, B8/B15 and DR3/DR4 showed significantly lower C-peptide concentrations (p less than 0.05) than patients without these HLA antigens. |
| 471 | 3545954 | Twelve patients who were positive for both DR3 and DR4 and 23 patients who were DR3/DR4 negative were followed with repeated C-peptide determinations during a period of three years. |
| 472 | 3545954 | The C-peptide concentrations of the DR3/DR4 positive patients decreased during this period, whereas there was no change in C-peptide levels in the DR3/DR4 negative patients. |
| 473 | 3545954 | The Type 1 diabetic patients showed a typical HLA pattern, with increased frequencies of B15, DR3, DR4, B8/B15 and DR3/DR4 and decreased frequencies of B7 and DR2. |
| 474 | 3545954 | The Type 2 diabetic patients could be distinguished from blood donors by increased frequencies of Cw4, DR4, DR5 and DR3/DR4, and from Type 1 diabetic patients by increased frequencies of B7, DR2, DR5 and decreased frequency of A9, Bw22 and DR4. |
| 475 | 3545954 | Age at onset and body mass index were unrelated to HLA antigens, but the Type 2 diabetic patients with HLA-Cw4, DR5 and DR6 showed a strong family history for Type 2 diabetes. |
| 476 | 3545954 | Type 2 diabetic patients with HLA-B8, DR4, B8/B15 and DR3/DR4 showed significantly lower C-peptide concentrations (p less than 0.05) than patients without these HLA antigens. |
| 477 | 3545954 | Twelve patients who were positive for both DR3 and DR4 and 23 patients who were DR3/DR4 negative were followed with repeated C-peptide determinations during a period of three years. |
| 478 | 3545954 | The C-peptide concentrations of the DR3/DR4 positive patients decreased during this period, whereas there was no change in C-peptide levels in the DR3/DR4 negative patients. |
| 479 | 3545954 | The Type 1 diabetic patients showed a typical HLA pattern, with increased frequencies of B15, DR3, DR4, B8/B15 and DR3/DR4 and decreased frequencies of B7 and DR2. |
| 480 | 3545954 | The Type 2 diabetic patients could be distinguished from blood donors by increased frequencies of Cw4, DR4, DR5 and DR3/DR4, and from Type 1 diabetic patients by increased frequencies of B7, DR2, DR5 and decreased frequency of A9, Bw22 and DR4. |
| 481 | 3545954 | Age at onset and body mass index were unrelated to HLA antigens, but the Type 2 diabetic patients with HLA-Cw4, DR5 and DR6 showed a strong family history for Type 2 diabetes. |
| 482 | 3545954 | Type 2 diabetic patients with HLA-B8, DR4, B8/B15 and DR3/DR4 showed significantly lower C-peptide concentrations (p less than 0.05) than patients without these HLA antigens. |
| 483 | 3545954 | Twelve patients who were positive for both DR3 and DR4 and 23 patients who were DR3/DR4 negative were followed with repeated C-peptide determinations during a period of three years. |
| 484 | 3545954 | The C-peptide concentrations of the DR3/DR4 positive patients decreased during this period, whereas there was no change in C-peptide levels in the DR3/DR4 negative patients. |
| 485 | 3545954 | The Type 1 diabetic patients showed a typical HLA pattern, with increased frequencies of B15, DR3, DR4, B8/B15 and DR3/DR4 and decreased frequencies of B7 and DR2. |
| 486 | 3545954 | The Type 2 diabetic patients could be distinguished from blood donors by increased frequencies of Cw4, DR4, DR5 and DR3/DR4, and from Type 1 diabetic patients by increased frequencies of B7, DR2, DR5 and decreased frequency of A9, Bw22 and DR4. |
| 487 | 3545954 | Age at onset and body mass index were unrelated to HLA antigens, but the Type 2 diabetic patients with HLA-Cw4, DR5 and DR6 showed a strong family history for Type 2 diabetes. |
| 488 | 3545954 | Type 2 diabetic patients with HLA-B8, DR4, B8/B15 and DR3/DR4 showed significantly lower C-peptide concentrations (p less than 0.05) than patients without these HLA antigens. |
| 489 | 3545954 | Twelve patients who were positive for both DR3 and DR4 and 23 patients who were DR3/DR4 negative were followed with repeated C-peptide determinations during a period of three years. |
| 490 | 3545954 | The C-peptide concentrations of the DR3/DR4 positive patients decreased during this period, whereas there was no change in C-peptide levels in the DR3/DR4 negative patients. |
| 491 | 3545954 | The Type 1 diabetic patients showed a typical HLA pattern, with increased frequencies of B15, DR3, DR4, B8/B15 and DR3/DR4 and decreased frequencies of B7 and DR2. |
| 492 | 3545954 | The Type 2 diabetic patients could be distinguished from blood donors by increased frequencies of Cw4, DR4, DR5 and DR3/DR4, and from Type 1 diabetic patients by increased frequencies of B7, DR2, DR5 and decreased frequency of A9, Bw22 and DR4. |
| 493 | 3545954 | Age at onset and body mass index were unrelated to HLA antigens, but the Type 2 diabetic patients with HLA-Cw4, DR5 and DR6 showed a strong family history for Type 2 diabetes. |
| 494 | 3545954 | Type 2 diabetic patients with HLA-B8, DR4, B8/B15 and DR3/DR4 showed significantly lower C-peptide concentrations (p less than 0.05) than patients without these HLA antigens. |
| 495 | 3545954 | Twelve patients who were positive for both DR3 and DR4 and 23 patients who were DR3/DR4 negative were followed with repeated C-peptide determinations during a period of three years. |
| 496 | 3545954 | The C-peptide concentrations of the DR3/DR4 positive patients decreased during this period, whereas there was no change in C-peptide levels in the DR3/DR4 negative patients. |
| 497 | 3556283 | The 1-yr incidence of insulin-dependent diabetes mellitus (IDDM) in a population of the Piedmont and Aosta Valley area of Italy was recorded. |
| 498 | 3556283 | Anti-virus antibodies (e.g., Coxsackie B1-6, mumps, cytomegalovirus), islet cell antibodies (ICAs), and HLA-A, -B, -C, and -DR were determined in 74 IDDM patients (38 males, 36 females) and in controls. |
| 499 | 3556283 | ICA frequency was significantly higher in DR3/DR4 heterozygote patients than in patients without DR3 and DR4. |
| 500 | 3569864 | A significantly increased sharing of HLA haplotypes was seen when the index sib was DR3/DR4 compared to those of other genotypes (68% versus 37% sharing 2 haplotypes, p less than .01). |
| 501 | 3701514 | Six had HLA-B8 and -DR3 antigens, and one had B15 and -DR4 phenotypes. |
| 502 | 3701514 | In most patients, a gluten-free diet had little effect on insulin dosage, urinary excretion of glucose, or serum level of hemoglobin A1. |
| 503 | 3726861 | The expected association with B8, B18, Bw62, DR3 and DR4 was observed as well as an excess of DR3/4 heterozygotes. |
| 504 | 3774753 | Using the HLA-DR4 association with two distinct diseases, IDDM and JRA, as a model, we can conclude the following: There are at least seven distinct haplotypes which share the HLA DR4 specificity; these haplotypes include six alleles at the DR-beta genetic locus. |
| 505 | 3774753 | DR4+ IDDM is most closely associated with the DQ 3.2 allele at DQ-beta; DR4+ JRA, on the other hand, appears to be highly associated with rare alleles at DR-beta, but not DQ. |
| 506 | 3774753 | Using the HLA-DR4 association with two distinct diseases, IDDM and JRA, as a model, we can conclude the following: There are at least seven distinct haplotypes which share the HLA DR4 specificity; these haplotypes include six alleles at the DR-beta genetic locus. |
| 507 | 3774753 | DR4+ IDDM is most closely associated with the DQ 3.2 allele at DQ-beta; DR4+ JRA, on the other hand, appears to be highly associated with rare alleles at DR-beta, but not DQ. |
| 508 | 3856541 | Breakdown of data by age of diagnosis of disease showed no increase in the frequency of BfF1 and GLO1-2 but an increase of HLA DR3 and DR4 in patients with early onset diabetes. |
| 509 | 3862360 | Singaporean Chinese IDDM was significantly associated with AW33, BW58, DR3 and DR4. |
| 510 | 3862360 | In the less than or equal to 10 years subgroup, the significant association were either DR3/DRW9, DR3/DR4 or DR3/BLANK. |
| 511 | 3862360 | Singaporean Chinese IDDM was significantly associated with AW33, BW58, DR3 and DR4. |
| 512 | 3862360 | In the less than or equal to 10 years subgroup, the significant association were either DR3/DRW9, DR3/DR4 or DR3/BLANK. |
| 513 | 3863777 | We report a combined segregation and linkage analysis of a Danish sample of 216 insulin-dependent diabetes mellitus (IDDM) nuclear families: of these 216, twenty multiplex families were haplotyped regarding HLA-DR and -B markers. |
| 514 | 3863777 | Particularly strong, positive haplotype associations were found for the DR3,B8, DR3,B18, and DR4,B15 haplotypes, but detailed analyses showed that neither these particular haplotypes nor the DR3 and DR4 haplotypes in general could entirely explain the HLA-associated susceptibility. |
| 515 | 3876922 | Progressive autoimmune beta cell insufficiency: occurrence in the absence of high-risk HLA alleles DR3, DR4. |
| 516 | 3880963 | Her HLA typing showed the following antigens: A1, A28, B8, B12 (44), BW4, BW6 DR3, and DR4. |
| 517 | 3881821 | 140 type 1 diabetics from Basle and vicinity were HLA-typed. 89% had HLA-haplotypes DR3, DR4, or DR3/DR4. |
| 518 | 3881821 | Compared to the latter, the relatives had a significantly diminished prevalence of the HLA DR3/DR4 combination. |
| 519 | 3881821 | 140 type 1 diabetics from Basle and vicinity were HLA-typed. 89% had HLA-haplotypes DR3, DR4, or DR3/DR4. |
| 520 | 3881821 | Compared to the latter, the relatives had a significantly diminished prevalence of the HLA DR3/DR4 combination. |
| 521 | 3887826 | HLA -B8, -B, -DR3 and -DR4 genotypes, low C4 complement concentrations and islet cell autoantibodies were detected at the time of diagnosis and 1 year later diabetes mellitus developed. |
| 522 | 3888064 | Histocompatibility region genes are major determinants of genetic susceptibility, and more than 90% of Type I individuals express HLA alleles DR3 or DR4. |
| 523 | 3896215 | The distribution of HLA types was not significantly different from a control population, with no increase in DR3 or DR4. |
| 524 | 3914156 | No differences were observed in the frequency of DR3 and DR4 antigens in the two groups but diabetics who developed a remission bore the A 19.2 antigen (9/31 vs 1/16) and the B18 one (11/31 vs 1/16) more frequently, A 19.2 and B18 being associated in 7 cases of this group. |
| 525 | 3935724 | Immunoglobulin heavy and light chain genes are often discussed as susceptibility genes for insulin dependent (type 1) diabetes mellitus (IDDM) in addition to HLA-DR3 and DR4. |
| 526 | 3935724 | While DR3 and DR4 antigens and DR3/DR4 heterozygotes occur significantly more often among diabetics than among normal controls, their Gm allotype frequencies are very similar. |
| 527 | 3935724 | An interaction between special Gm allotypes and phenotypes, on the one side, and DR3, DR4 or DR3, 4 on the other side could not be demonstrated. |
| 528 | 3935724 | Immunoglobulin heavy and light chain genes are often discussed as susceptibility genes for insulin dependent (type 1) diabetes mellitus (IDDM) in addition to HLA-DR3 and DR4. |
| 529 | 3935724 | While DR3 and DR4 antigens and DR3/DR4 heterozygotes occur significantly more often among diabetics than among normal controls, their Gm allotype frequencies are very similar. |
| 530 | 3935724 | An interaction between special Gm allotypes and phenotypes, on the one side, and DR3, DR4 or DR3, 4 on the other side could not be demonstrated. |
| 531 | 6332753 | Analysis of HLA and C4 allotypes suggested that Type 1 diabetes was associated with only certain DR3- and DR4-containing supratypes. |
| 532 | 6332752 | When comparing the distribution of the phenotype C4BQ0 in Type 1 diabetic patients and normal control subjects, the difference was significant in patients bearing DR3 or DR4 (56% and 25%, respectively, p less than 0.003). |
| 533 | 6333238 | Insulin dependent diabetes mellitus (IDDM) is closely associated with special MHC gene products. |
| 534 | 6333238 | The increased diabetic risk for the identical siblings of DR3, DR4-positive patients offers a good opportunity of studying genetically influenced immune deviations in the prediabetic phase which result in the suppression and destruction of Beta cells and finally in the manifestation of diabetes. |
| 535 | 6334991 | Two novel analytic methods to evaluate the roles of the HLA alleles of the human major histocompatibility complex in disease predisposition have been formulated and applied to insulin-dependent diabetes mellitus (IDDM). |
| 536 | 6334991 | In Caucasian populations, after consideration of the predisposing effect of the antigens DR3 and DR4, the protective effect of DR2 in predisposition is demonstrated. |
| 537 | 6335238 | Human lymphocyte antigen (HLA)-DR-typing was performed in 117 insulin-dependent diabetics with age at onset between 0.5 and 17 years (mean +/- SD, 9.0 +/- 3.9); 115 of 117 patients were DR3- and/or DR4-positive. |
| 538 | 6335238 | A comparison between DR3 and DR4 patients showed that DR4 patients manifested a seasonal variation of onset (most common onset during spring and autumn), had more severe signs and symptoms of the disease at onset, and were less likely to have a partial remission than patients with DR3. |
| 539 | 6336275 | Those at risk are adolescent females with HLA DR3 and DR4 as well as those with limited joint mobility. |
| 540 | 6339368 | Among the conditions which have been shown to be HLA-associated more recently, four deserves special mention: (i) maternal immunization against the Zwa antigen because this is a good candidate for an antigen-specific Ir gene action; (ii) IgA deficiency in blood donors because this is a non-antigen-specific immunodeficiency; (iii) idiopathic hemochromatosis and (iv) congenital adrenal hyperplasia due to 21-OH deficiency because immune mechanisms are unlikely to be involved. |
| 541 | 6339368 | HLA plays a definite and strong role in the susceptibility to IDDM, but simple genetic models (dominant, recessive, and intermediate) have been made unlikely on the basis of HLA results; the hypothesis that there are two different susceptibility genes within the HLA system still remains viable, but the demonstration of clinical heterogeneity and/or (better) of different pathogenetic pathways for DR3- and DR4-associated IDDM is required to substantiate it. |
| 542 | 6341762 | In order to test for intrafamilial constancy and intergroup variation, we compared simplex with multiplex families, HLA identical and non identical siblings within families, as well as groups of families characterized by different DR alleles (DR3, DR4, and DR3/DR4) for various immunologic and clinical characteristics. |
| 543 | 6373322 | A high proportion of twins, but not of IGT subjects, had HLA DR3 or DR4 antigens which seem to confer genetic susceptibility to the development of IDDM. |
| 544 | 6373322 | In the majority of DR3/DR4 twins, ICSA were also present. |
| 545 | 6373322 | A high proportion of twins, but not of IGT subjects, had HLA DR3 or DR4 antigens which seem to confer genetic susceptibility to the development of IDDM. |
| 546 | 6373322 | In the majority of DR3/DR4 twins, ICSA were also present. |
| 547 | 6373451 | The frequency and significance of cytoplasmic pancreatic alpha cell autoantibodies (ACA) were investigated in 2102 healthy controls, 879 patients with insulin-dependent diabetes mellitus (IDDM) who were negative for islet cell autoantibodies (ICA), and 1567 relatives of IDDM patients. |
| 548 | 6373451 | ACA were found in approximately 1 in 200 people of all ages and were not significantly associated with IDDM, the IDDM-associated HLA phenotypes DR3 and DR4, or thyrogastric or adrenal autoantibodies. |
| 549 | 6383905 | There is heterogeneity within insulin-dependent diabetes mellitus (IDDM), and it has been suggested that the presence of the HLA-DR specificities DR3 and DR4 define two subsets of IDDM with clear differences in their immune response to therapeutic insulin. |
| 550 | 6383905 | To test this hypothesis, we have prospectively studies the development of insulin binding antibody (IBA) in 54 subjects with newly diagnosed, classical childhood IDDM, determined seven binding constants of their IBA, and measured the presence or absence of pancreatic polypeptide-binding antibodies after 1 yr of therapy with insulin. |
| 551 | 6383905 | There were no relationships between insulin and pancreatic polypeptide antibodies and the DR3 or DR4 specificities whether these specificities were tested for alone or in combination, comparing the presence and absence of DR3 and DR4 and comparing DR3 with DR4, except that of the 33% of all subjects who developed antibodies binding pancreatic polypeptide by 1 yr, none possessed the DR3 specificity alone (P = 0.018). |
| 552 | 6383905 | Thus, the hypothesis that the HLA-DR3 and -DR4 specificities are major determinants of IBA formation and, therefore, define important subsets of childhood IDDM in terms of immune response to therapeutic insulin is not substantiated by this study. |
| 553 | 6383905 | There is heterogeneity within insulin-dependent diabetes mellitus (IDDM), and it has been suggested that the presence of the HLA-DR specificities DR3 and DR4 define two subsets of IDDM with clear differences in their immune response to therapeutic insulin. |
| 554 | 6383905 | To test this hypothesis, we have prospectively studies the development of insulin binding antibody (IBA) in 54 subjects with newly diagnosed, classical childhood IDDM, determined seven binding constants of their IBA, and measured the presence or absence of pancreatic polypeptide-binding antibodies after 1 yr of therapy with insulin. |
| 555 | 6383905 | There were no relationships between insulin and pancreatic polypeptide antibodies and the DR3 or DR4 specificities whether these specificities were tested for alone or in combination, comparing the presence and absence of DR3 and DR4 and comparing DR3 with DR4, except that of the 33% of all subjects who developed antibodies binding pancreatic polypeptide by 1 yr, none possessed the DR3 specificity alone (P = 0.018). |
| 556 | 6383905 | Thus, the hypothesis that the HLA-DR3 and -DR4 specificities are major determinants of IBA formation and, therefore, define important subsets of childhood IDDM in terms of immune response to therapeutic insulin is not substantiated by this study. |
| 557 | 6383919 | Several patterns of HLA-DR expression were noted (DR3/DR4, DR3/DR3, DR3/x, DR3/DR1, DR4/x, DR4/DR7, DR5/DR7, DR1/DR7 and DR1/DR2). |
| 558 | 6385308 | In insulin-dependent diabetes mellitus (IDDM) there is a strong link with the HLA system with regard to the inheritance of 'susceptible' diabetic genes, especially the DR3 and DR4 alleles. |
| 559 | 6385308 | Non-insulin-dependent diabetes mellitus (NIDDM) has no clear HLA link, but has been shown in studies of twins to have a stronger genetic basis than IDDM. |
| 560 | 6388459 | Present knowledge regarding the HLA system and the association between HLA antigens and insulin-dependent type 1 diabetes mellitus (IDDM) is reviewed. |
| 561 | 6388459 | The frequency of HLA antigens B7, B8 (in linkage disequilibrium with DR3), B15 (in linkage disequilibrium with DR4) and B18 was examined in comparison with a Piemontese control group. |
| 562 | 6392072 | To investigate whether the development of islet-cell antibodies (ICA) in the course of mumps infection is associated with a "diabetes-like" immunogenetic condition, 45 children with mumps complications as well as 56 children with insulin-dependent diabetes mellitus (IDDM) were typed for HLA ABC and DR antigens. |
| 563 | 6392072 | In the IDDM group, significant deviations from antigen frequencies of normal controls were observed for HLA Bw39, DR2, DR3, and DR4. |
| 564 | 6393434 | The patients included 296 subjects with insulin-dependent diabetes (IDDM) and 320 with noninsulin dependent diabetes (NIDDM). |
| 565 | 6393434 | Concerning the relationship between HLA-type and ICA in IDDM, there was a tendency for the prevalence of BW54, DR4 and MT3 of HLA to be higher in the ICA-negative group than in the ICA-positive group or the non-diabetic group. |
| 566 | 6402059 | In both the concordant and discordant groups there was a high prevalence of the antigens DR3 and DR4, a low prevalence of DR5 and DR7, and a virtual absence of DR2. |
| 567 | 6402059 | The heterozygous phenotype DR3,DR4 was more prevalent in concordant than discordant pairs. |
| 568 | 6402059 | These findings suggest that possession of both DR3 and DR4 antigens confers a greater genetic predisposition to insulin-dependent diabetes than does the possession of either antigen alone. |
| 569 | 6402059 | In both the concordant and discordant groups there was a high prevalence of the antigens DR3 and DR4, a low prevalence of DR5 and DR7, and a virtual absence of DR2. |
| 570 | 6402059 | The heterozygous phenotype DR3,DR4 was more prevalent in concordant than discordant pairs. |
| 571 | 6402059 | These findings suggest that possession of both DR3 and DR4 antigens confers a greater genetic predisposition to insulin-dependent diabetes than does the possession of either antigen alone. |
| 572 | 6402059 | In both the concordant and discordant groups there was a high prevalence of the antigens DR3 and DR4, a low prevalence of DR5 and DR7, and a virtual absence of DR2. |
| 573 | 6402059 | The heterozygous phenotype DR3,DR4 was more prevalent in concordant than discordant pairs. |
| 574 | 6402059 | These findings suggest that possession of both DR3 and DR4 antigens confers a greater genetic predisposition to insulin-dependent diabetes than does the possession of either antigen alone. |
| 575 | 6402405 | HLA genotypic study of insulin-dependent diabetes the excess of DR3/DR4 heterozygotes allows rejection of the recessive hypothesis. |
| 576 | 6402405 | The genetics of insulin-dependent diabetes mellitus (IDDM) is currently an area of controversy, with some investigators proposing heterogeneity within the HLA region and even the existence of non-HLA-linked susceptibility genes, and others maintaining that a simple autosomal recessive gene linked to HLA with reduced penetrance is an adequate explanation. |
| 577 | 6402405 | It is shown that if the number of DR3/DR4 heterozygotes in a diabetic population exceeds the combined sum of DR3/3 and DR4/4 homozygotes in that same diabetic population, then a recessive mode of inheritance can be rejected. |
| 578 | 6402405 | HLA genotypic study of insulin-dependent diabetes the excess of DR3/DR4 heterozygotes allows rejection of the recessive hypothesis. |
| 579 | 6402405 | The genetics of insulin-dependent diabetes mellitus (IDDM) is currently an area of controversy, with some investigators proposing heterogeneity within the HLA region and even the existence of non-HLA-linked susceptibility genes, and others maintaining that a simple autosomal recessive gene linked to HLA with reduced penetrance is an adequate explanation. |
| 580 | 6402405 | It is shown that if the number of DR3/DR4 heterozygotes in a diabetic population exceeds the combined sum of DR3/3 and DR4/4 homozygotes in that same diabetic population, then a recessive mode of inheritance can be rejected. |
| 581 | 6407886 | HLA-DR and MT1, MT2, MT3 genotypes have been investigated in 123 Type 1 (insulin-dependent) diabetic subjects and their families. |
| 582 | 6407886 | Almost 51% of the probands were DR3, DR4 heterozygotes. |
| 583 | 6407886 | The DR antigen combinations of the parents leading to DR3, DR4 heterozygous and to DR3 and DR4 homozygous offspring were analysed. |
| 584 | 6407886 | There was a marked increase in DR3, DR4 heterozygosity, but no increase in homozygosity for these antigens compared with the expected frequencies. |
| 585 | 6407886 | In each case, the other inherited allele was DR3 or DR4. |
| 586 | 6407886 | HLA-DR and MT1, MT2, MT3 genotypes have been investigated in 123 Type 1 (insulin-dependent) diabetic subjects and their families. |
| 587 | 6407886 | Almost 51% of the probands were DR3, DR4 heterozygotes. |
| 588 | 6407886 | The DR antigen combinations of the parents leading to DR3, DR4 heterozygous and to DR3 and DR4 homozygous offspring were analysed. |
| 589 | 6407886 | There was a marked increase in DR3, DR4 heterozygosity, but no increase in homozygosity for these antigens compared with the expected frequencies. |
| 590 | 6407886 | In each case, the other inherited allele was DR3 or DR4. |
| 591 | 6407886 | HLA-DR and MT1, MT2, MT3 genotypes have been investigated in 123 Type 1 (insulin-dependent) diabetic subjects and their families. |
| 592 | 6407886 | Almost 51% of the probands were DR3, DR4 heterozygotes. |
| 593 | 6407886 | The DR antigen combinations of the parents leading to DR3, DR4 heterozygous and to DR3 and DR4 homozygous offspring were analysed. |
| 594 | 6407886 | There was a marked increase in DR3, DR4 heterozygosity, but no increase in homozygosity for these antigens compared with the expected frequencies. |
| 595 | 6407886 | In each case, the other inherited allele was DR3 or DR4. |
| 596 | 6407886 | HLA-DR and MT1, MT2, MT3 genotypes have been investigated in 123 Type 1 (insulin-dependent) diabetic subjects and their families. |
| 597 | 6407886 | Almost 51% of the probands were DR3, DR4 heterozygotes. |
| 598 | 6407886 | The DR antigen combinations of the parents leading to DR3, DR4 heterozygous and to DR3 and DR4 homozygous offspring were analysed. |
| 599 | 6407886 | There was a marked increase in DR3, DR4 heterozygosity, but no increase in homozygosity for these antigens compared with the expected frequencies. |
| 600 | 6407886 | In each case, the other inherited allele was DR3 or DR4. |
| 601 | 6411398 | HLA-A and -B typing performed on 231 IDDM individuals and 268 controls from the southeastern U.S. showed significant increases with IDDM in A2, B8, B15 and B18, and significant decreases in Aw23, B7, B14 and B17. |
| 602 | 6411398 | Using the method of Curie-Cohen, no significant increases in risk were found for the B8/B15 or DR3/DR4 heterozygotes when compared to the respective homozygotes. |
| 603 | 6411398 | There was a significant increase in B15 and DR4 in those with onset before age 20. |
| 604 | 6411398 | HLA-A and -B typing performed on 231 IDDM individuals and 268 controls from the southeastern U.S. showed significant increases with IDDM in A2, B8, B15 and B18, and significant decreases in Aw23, B7, B14 and B17. |
| 605 | 6411398 | Using the method of Curie-Cohen, no significant increases in risk were found for the B8/B15 or DR3/DR4 heterozygotes when compared to the respective homozygotes. |
| 606 | 6411398 | There was a significant increase in B15 and DR4 in those with onset before age 20. |
| 607 | 6418443 | Ninety-seven percent of Type 1 diabetic patients belonging to the Barts-Windsor family study possess either DR3 or DR4 and about 50% possess both these antigens. |
| 608 | 6418443 | This excess of DR3, DR4 heterozygosity can be best explained by postulating two different susceptibility genes which react in an interactive way. |
| 609 | 6418443 | No increase in DR3 or DR4 homozygosity is found, nor is there an increase in recombination frequency in these families. |
| 610 | 6418443 | Ninety-seven percent of Type 1 diabetic patients belonging to the Barts-Windsor family study possess either DR3 or DR4 and about 50% possess both these antigens. |
| 611 | 6418443 | This excess of DR3, DR4 heterozygosity can be best explained by postulating two different susceptibility genes which react in an interactive way. |
| 612 | 6418443 | No increase in DR3 or DR4 homozygosity is found, nor is there an increase in recombination frequency in these families. |
| 613 | 6418443 | Ninety-seven percent of Type 1 diabetic patients belonging to the Barts-Windsor family study possess either DR3 or DR4 and about 50% possess both these antigens. |
| 614 | 6418443 | This excess of DR3, DR4 heterozygosity can be best explained by postulating two different susceptibility genes which react in an interactive way. |
| 615 | 6418443 | No increase in DR3 or DR4 homozygosity is found, nor is there an increase in recombination frequency in these families. |
| 616 | 6443704 | Initial researches, performed until now almost exclusively upon diabetics treated with conventional heterologous insulin, seem to indicate a positive relationship between haplotype HLA - B15 - DR4 and an elevated immune response, whereas haplotypes HLA - B8 - DR3 and HLA - B18 - DR3 might protect against the formation of anti-insulin antibodies. |
| 617 | 6443704 | Antigens D/DR3 and D/DR4 are known to be primitively associated to susceptibility for type I diabetes, whereas antigens B8, B15, B18 are secondarily associated to the rise in frequency of DR3 and DR4 for the "linkage disequilibrium" existing between alleles of B and D loci. |
| 618 | 6443704 | A study of the frequencies of various HLA-B antigens in both groups of patients, in regard to a control group of piemontese population, in relation to the intensity of association (relative risk) and to the statistical importance of frequencies, shows only a possible protective effect of the HLA-B18 phenotype (linkage disequilibrium with HLA - DR3) towards the production of anti-insulin antibodies and hyperimmune clinical manifestations, such as allergy. |
| 619 | 6443704 | Initial researches, performed until now almost exclusively upon diabetics treated with conventional heterologous insulin, seem to indicate a positive relationship between haplotype HLA - B15 - DR4 and an elevated immune response, whereas haplotypes HLA - B8 - DR3 and HLA - B18 - DR3 might protect against the formation of anti-insulin antibodies. |
| 620 | 6443704 | Antigens D/DR3 and D/DR4 are known to be primitively associated to susceptibility for type I diabetes, whereas antigens B8, B15, B18 are secondarily associated to the rise in frequency of DR3 and DR4 for the "linkage disequilibrium" existing between alleles of B and D loci. |
| 621 | 6443704 | A study of the frequencies of various HLA-B antigens in both groups of patients, in regard to a control group of piemontese population, in relation to the intensity of association (relative risk) and to the statistical importance of frequencies, shows only a possible protective effect of the HLA-B18 phenotype (linkage disequilibrium with HLA - DR3) towards the production of anti-insulin antibodies and hyperimmune clinical manifestations, such as allergy. |
| 622 | 6541983 | To illustrate the method, it is applied to two specific diseases, insulin dependent diabetes mellitus (IDDM) and gluten-sensitive enteropathy (GSE), and a specific locus, the HLA gene complex. |
| 623 | 6541983 | A possible reason for these differences is the markedly increased disease susceptibility of the DR3/DR4 heterozygote for IDDM. |
| 624 | 6573128 | Heterozygous expression of insulin-dependent diabetes mellitus (IDDM) determinants in the HLA system. |
| 625 | 6573128 | HLA phenotypes of cases with insulin-dependent diabetes mellitus (IDDM) and identity by descent of HLA haplotypes in affected sib-pairs support an intermediate model in which morbid risk is increased by one HLA-linked IDDM determinant, and greatly increased by two determinants, which may be qualitatively different in DR3 and DR4 haplotypes. |
| 626 | 6573128 | Linkage analysis allowing for gametic disequilibrium reveals no recombination in pedigrees with a DR3/DR4 propositus, but spurious recombination in the remaining pedigrees. |
| 627 | 6573128 | Heterozygous expression of insulin-dependent diabetes mellitus (IDDM) determinants in the HLA system. |
| 628 | 6573128 | HLA phenotypes of cases with insulin-dependent diabetes mellitus (IDDM) and identity by descent of HLA haplotypes in affected sib-pairs support an intermediate model in which morbid risk is increased by one HLA-linked IDDM determinant, and greatly increased by two determinants, which may be qualitatively different in DR3 and DR4 haplotypes. |
| 629 | 6573128 | Linkage analysis allowing for gametic disequilibrium reveals no recombination in pedigrees with a DR3/DR4 propositus, but spurious recombination in the remaining pedigrees. |
| 630 | 6573286 | A group of patients with Type 1 (insulin-dependent) diabetes mellitus was investigated for HLA-A, B and DR antigens as well as C4 and factor B polymorphism. |
| 631 | 6573286 | A significant excess of DR3/DR4 heterozygotes was observed (27% versus 17% by Hardy-Weinberg expectation). |
| 632 | 6584368 | HLA-A, B, C and DR antigens in young South African blacks with Type 1 (insulin-dependent) diabetes mellitus. |
| 633 | 6584368 | DR3/DR4 heterozygosity was associated with a greater relative risk for developing Type 1 diabetes mellitus (3.7) than the presence of DR3 alone (relative risk 1.6). |
| 634 | 6586708 | Three diabetic haplotypes were confirmed to occur frequently among affected sibs: (a) A1, B8, BFS, C2.1, C4AQO , C4B1 ,DR3, GLO2 ; (b) Aw30, Cw5 ,B18,BFF1,C2.1, C4A3 , C4BQO ,DR3, GLO2 ; (c) A2,Cw3, B15,BFS, C2.1, C4A3 , C4B3 , DR4,GLO1. |
| 635 | 6589235 | The Pittsburgh Insulin-Dependent Diabetes Mellitus (IDDM) study. |
| 636 | 6589235 | The relationships between HLA antigens, sex, age at diagnosis, season of onset and insulin-dependent diabetes mellitus (IDDM) were studied in a consecutive admissions series of newly-diagnosed IDDM patients at Children's Hospital of Pittsburgh. |
| 637 | 6589235 | In agreement with the findings of others, the strongest positive associations between IDDM and HLA antigens were seen with DR3 and DR4 (odds ratios (OR) of 3.5 and 4.4, respectively), while a very strong negative association was observed with DR2 (OR of 0.1). |
| 638 | 6592118 | This supports the hypothesis of two different risk factors associated with DR3 and DR4. |
| 639 | 6592119 | Twenty probands carried DR2, in 11 or whom (55%) it was found in combination with either DR3 or DR4. |
| 640 | 6592119 | However, when the DR2 transmission was analysed separately for parents bearing DR2 with DR3, DR4 or another DR allele, it appeared that DR2 transmission to affected offspring was random when the parents carried neither DR3 or DR4, the transmission deficit being due to over-transmission of DR3 and DR4. |
| 641 | 6592119 | Twenty probands carried DR2, in 11 or whom (55%) it was found in combination with either DR3 or DR4. |
| 642 | 6592119 | However, when the DR2 transmission was analysed separately for parents bearing DR2 with DR3, DR4 or another DR allele, it appeared that DR2 transmission to affected offspring was random when the parents carried neither DR3 or DR4, the transmission deficit being due to over-transmission of DR3 and DR4. |
| 643 | 6608876 | Although association with the DR3 and DR4 alleles is quite strong, pleiotropy with regard to these alleles is unlikely. |
| 644 | 6610167 | Insulin administration (once or twice a day) and glycemic control as reflected by hemoglobin A1C were identical in those with progression and in those with no progression of retinopathy. |
| 645 | 6610167 | Human lymphocyte antigen (HLA) types DR3 and DR4 in combination occurred more frequently (P less than .001) in those with progression of retinopathy than in those without progression. |
| 646 | 6610167 | Teenaged , female, insulin-dependent diabetics with both HLA DR3, and DR4, were at increased risk for developing proliferative retinopathy. |
| 647 | 6610167 | Insulin administration (once or twice a day) and glycemic control as reflected by hemoglobin A1C were identical in those with progression and in those with no progression of retinopathy. |
| 648 | 6610167 | Human lymphocyte antigen (HLA) types DR3 and DR4 in combination occurred more frequently (P less than .001) in those with progression of retinopathy than in those without progression. |
| 649 | 6610167 | Teenaged , female, insulin-dependent diabetics with both HLA DR3, and DR4, were at increased risk for developing proliferative retinopathy. |
| 650 | 6755530 | The subtype of diabetes related to DR4/B15 does not appear to predispose to coeliac disease. |
| 651 | 6814007 | By contrast, the observed frequency of patients homozygous for DR3 or DR4 was not increased, but even slightly decreased. |
| 652 | 6814007 | The data support a model of inheritance comprising at least two closely linked specifically "diabetic" loci (most of the time marked by B18, BfF1, DR3 and B15, BfS, DR4) and a non-specifically "diabetic" haplotype favouring auto-immunisation (most of the time marked by B8, BfS, DR3). |
| 653 | 6814007 | By contrast, the observed frequency of patients homozygous for DR3 or DR4 was not increased, but even slightly decreased. |
| 654 | 6814007 | The data support a model of inheritance comprising at least two closely linked specifically "diabetic" loci (most of the time marked by B18, BfF1, DR3 and B15, BfS, DR4) and a non-specifically "diabetic" haplotype favouring auto-immunisation (most of the time marked by B8, BfS, DR3). |
| 655 | 6814597 | The difference in the binding capacity of beef insulin by the high affinity antibodies between the groups with DR3 and DR4 antigens was less pronounced but still significant. |
| 656 | 6814597 | If extended to human insulin and different HLA-DR and HLA-B antigen patterns, these finding should help in the therapeutic selection of the appropriate insulin and thus reduce the induction of an anti-insulin response in patients with diabetes. |
| 657 | 6944299 | On the other hand, the frequency of A26, B18, and Bw38 was increased in Ashkenazi patients, but not in non-Ashkenazim, who in turn showed an increase for Bw51. |
| 658 | 6944299 | There was a typical excess of DR3/DR4 heterozygotes in both patient groups. |
| 659 | 6950819 | Histocompatibility (HLA) antigens and genotypes B, D and DR were studied in large sample of Caucasian insulin dependent diabetic (IDD) probands. |
| 660 | 6950819 | The associations between IDD and B8, B15, Dw3, Dw4, and DR3, and DR4 were measured by relative risks (RR) and delta values. |
| 661 | 6951830 | We studied 102 randomly ascertained probands from the Upper Midwest United States with insulin-dependent diabetes mellitus (IDDM) with respect to both HLA-DR and Kidd (Jk) markers. |
| 662 | 6951830 | Based on our evidence that multiple genetic mechanisms may be involved in the etiology of IDDM the data were partitioned according to the HLA-DR phenotype, containing either two high risk antigens (DR3 or DR4) or not. |
| 663 | 6951830 | These results strongly suggest a complex model of IDDM inheritance involving, at least, one susceptibility locus in linkage disequilibrium with HLA DR3 and DR4 on chromosome 6, and a second locus in linkage disequilibrium with Jkb on chromosome 2. |
| 664 | 6951830 | We studied 102 randomly ascertained probands from the Upper Midwest United States with insulin-dependent diabetes mellitus (IDDM) with respect to both HLA-DR and Kidd (Jk) markers. |
| 665 | 6951830 | Based on our evidence that multiple genetic mechanisms may be involved in the etiology of IDDM the data were partitioned according to the HLA-DR phenotype, containing either two high risk antigens (DR3 or DR4) or not. |
| 666 | 6951830 | These results strongly suggest a complex model of IDDM inheritance involving, at least, one susceptibility locus in linkage disequilibrium with HLA DR3 and DR4 on chromosome 6, and a second locus in linkage disequilibrium with Jkb on chromosome 2. |
| 667 | 6979813 | The inclusion of HLA data in genetic studies of insulin-dependent diabetes mellitus (IDDM) has not led to conclusive segregation models for IDDM so far. |
| 668 | 6979813 | However, when the pedigrees were divided according to whether or not the proband had the heterozygous HLA-phenotype DR3/DR4, a maximum likelihood ratio test for heterogeneity was significant, with estimated recombination fractions of 0.0 and 0.0963 in HLA-DR3/DR4 pedigrees and the remaining pedigrees, respectively. |
| 669 | 7011215 | HLA-A, B, C, and DR-typing was performed in 51 children with insulin-dependent diabetes. |
| 670 | 7011215 | The combination of DR3 and DR4 was present in 37% of the diabetic children compared with only 4% of the controls. |
| 671 | 7021118 | Significantly positive associations of the disease with HLA DR3 and DR4 and a negative association with DR2 were found. |
| 672 | 7021118 | Positive and negative associations with the various HLA A, B and C antigens (A1, A2, B8, B15, B18, Cw3) are of a secondary nature due to strong genetic coupling with primarily associated DR alleles. |
| 673 | 7031028 | A very high association between ICA and DR3 and DR4 was encountered (chi 2 = 17, with two df); half of the patients positive for either one of these antigens were ICA positive. |
| 674 | 7031028 | These results indicate that ICA associates equally with DR3 and DR4, against the hypothesis that this expression of autoimmunity is more a characteristic of DR3- than of DR4-associated genetic susceptibility. |
| 675 | 7031028 | A very high association between ICA and DR3 and DR4 was encountered (chi 2 = 17, with two df); half of the patients positive for either one of these antigens were ICA positive. |
| 676 | 7031028 | These results indicate that ICA associates equally with DR3 and DR4, against the hypothesis that this expression of autoimmunity is more a characteristic of DR3- than of DR4-associated genetic susceptibility. |
| 677 | 7031653 | Insulin-dependent diabetes mellitus is often accompanied by manifestations of autoimmunity and is frequently associated with certain HLA haplotypes, predominantly DR3 and DR4. |
| 678 | 7031653 | The major histocompatibility antigens corresponding to the H-2 K,D molecules in mice, the H1-A in rats, and the HLA-A, -B, and -C in humans were precipitated from both islet and lymphocyte lysates and were accompanied by beta 2-microglobulin. |
| 679 | 7547572 | ALP, IGA, and PC had the highest 5-year graft survival rates (72.8%, 71.2%, and 68.5%, respectively) whereas HTN and NS, the lowest (51.8% and 46.0%, respectively). 2. |
| 680 | 7547572 | Despite having overall lower graft survival than Whites (p < 0.00001), there was no significant difference between Black and White 3-year graft survival for recipients with PC, ALP, IGA, and SLE. 4. |
| 681 | 7547572 | Whites expressing DR3 and DR4 and DR3 or DR4 alleles had better overall HLA matching (p < 0.001) and graft survival (75.4% and 70.7% versus 58.5% and 65.1%, p < 0.00001) than Blacks with similar DR expression. 8. |
| 682 | 7553076 | One of them was a control person having a family history of diabetes and genetic loci DR4/DR11. |
| 683 | 7660388 | Fifty-seven Thai IDDM patients were studied for HLA class I by LCT and HLA class II by LCT and PCR-RFLP. |
| 684 | 7660388 | In contrast, DQA1*0101, DRB3*0301, DR5 and DQ1 were significantly decreased with R.R. = 0.2, 0.2, 0.3 and 0.5 and Pc < 0.01, 0.05, 0.01 and 0.05, respectively. |
| 685 | 7660388 | However, DR3/DR4 genotype was increased only in female patients with a family history of DM and early onset. |
| 686 | 7706515 | HLA typing for DR3 and DR4 using artificial restriction fragment length polymorphism PCR from archival DNA. |
| 687 | 7726162 | Among patients with insulin-dependent diabetes mellitus (IDDM), an excess of DR3 and DR4 alleles is classically described when compared with the general population. |
| 688 | 7834558 | The HLA typing of both patients showed no relation to DR3 or DR4. |
| 689 | 7835212 | Fifty juvenile insulin dependent diabetes mellitus (JIDDM) patients of Tamil Nadu (South India) were typed for HLA-A, -B, -C, -DR, and -DQ, ESD, GLOI, C3 and HP polymorphisms. |
| 690 | 7835212 | The frequencies of B8, DR3, DR4, DR53 and DQ2 antigens of the HLA system were significantly higher in the patients than in controls (relative risk, RR = 4.81; 5.14; 3.98; 3.36 and 2.53, respectively). |
| 691 | 7835212 | However HLA-DR2, -DR5 and -DQ1, observed less frequently in the patient group, appear to play a role of protection against the disease (RR = 0.32; 0.30 and 0.20 respectively). |
| 692 | 7914753 | Type 1 (insulin-dependent) diabetes is strongly associated with the HLA genes encoding DR3 and DR4 and their associated DQ alleles. |
| 693 | 8058658 | The degree of the immunologic shifts was in direct correlation with the HLA A9 antigen expression, this relationship being the most marked in cases with the HLA DR3 and DR4. |
| 694 | 8093442 | Association of tumor necrosis factor (TNF) and class II major histocompatibility complex alleles with the secretion of TNF-alpha and TNF-beta by human mononuclear cells: a possible link to insulin-dependent diabetes mellitus. |
| 695 | 8093442 | We have investigated the correlation between different tumor necrosis factor (TNF) and class II major histocompatibility complex alleles in the lipopolysaccharide- or phytohemagglutinin-induced secretion of TNF-alpha and TNF-beta by human monocytes and peripheral blood mononuclear cells in 87 unrelated Danish male individuals. |
| 696 | 8093442 | Significant differences in TNF-alpha secretory capacity between TNF NcoI restriction fragment length polymorphisms, TNFa and TNFc microsatellite alleles and DR alleles were identified. |
| 697 | 8093442 | In a group of DR3/DR4 heterozygous patients with insulin-dependent diabetes mellitus (IDDM), the frequency of the TNFa2 allele was higher than in HLA-DR matched controls, whereas the TNFa6 allele was more frequent in control individuals. |
| 698 | 8093442 | In the DR3/DR4 heterozygous diabetic group 12/26 had the alleles combination DQw8, DR4 (Dw4), C4A3, TNFB*2, TNFa2, B15, whereas only 1/18 controls had this haplotype. |
| 699 | 8093442 | This diabetogenic haplotype is identical to the DR4 haplotype which correlates with a higher TNF-alpha response. |
| 700 | 8093442 | These observations suggest a direct role for the TNF locus in the pathogenesis of IDDM. |
| 701 | 8093442 | Association of tumor necrosis factor (TNF) and class II major histocompatibility complex alleles with the secretion of TNF-alpha and TNF-beta by human mononuclear cells: a possible link to insulin-dependent diabetes mellitus. |
| 702 | 8093442 | We have investigated the correlation between different tumor necrosis factor (TNF) and class II major histocompatibility complex alleles in the lipopolysaccharide- or phytohemagglutinin-induced secretion of TNF-alpha and TNF-beta by human monocytes and peripheral blood mononuclear cells in 87 unrelated Danish male individuals. |
| 703 | 8093442 | Significant differences in TNF-alpha secretory capacity between TNF NcoI restriction fragment length polymorphisms, TNFa and TNFc microsatellite alleles and DR alleles were identified. |
| 704 | 8093442 | In a group of DR3/DR4 heterozygous patients with insulin-dependent diabetes mellitus (IDDM), the frequency of the TNFa2 allele was higher than in HLA-DR matched controls, whereas the TNFa6 allele was more frequent in control individuals. |
| 705 | 8093442 | In the DR3/DR4 heterozygous diabetic group 12/26 had the alleles combination DQw8, DR4 (Dw4), C4A3, TNFB*2, TNFa2, B15, whereas only 1/18 controls had this haplotype. |
| 706 | 8093442 | This diabetogenic haplotype is identical to the DR4 haplotype which correlates with a higher TNF-alpha response. |
| 707 | 8093442 | These observations suggest a direct role for the TNF locus in the pathogenesis of IDDM. |
| 708 | 8093442 | Association of tumor necrosis factor (TNF) and class II major histocompatibility complex alleles with the secretion of TNF-alpha and TNF-beta by human mononuclear cells: a possible link to insulin-dependent diabetes mellitus. |
| 709 | 8093442 | We have investigated the correlation between different tumor necrosis factor (TNF) and class II major histocompatibility complex alleles in the lipopolysaccharide- or phytohemagglutinin-induced secretion of TNF-alpha and TNF-beta by human monocytes and peripheral blood mononuclear cells in 87 unrelated Danish male individuals. |
| 710 | 8093442 | Significant differences in TNF-alpha secretory capacity between TNF NcoI restriction fragment length polymorphisms, TNFa and TNFc microsatellite alleles and DR alleles were identified. |
| 711 | 8093442 | In a group of DR3/DR4 heterozygous patients with insulin-dependent diabetes mellitus (IDDM), the frequency of the TNFa2 allele was higher than in HLA-DR matched controls, whereas the TNFa6 allele was more frequent in control individuals. |
| 712 | 8093442 | In the DR3/DR4 heterozygous diabetic group 12/26 had the alleles combination DQw8, DR4 (Dw4), C4A3, TNFB*2, TNFa2, B15, whereas only 1/18 controls had this haplotype. |
| 713 | 8093442 | This diabetogenic haplotype is identical to the DR4 haplotype which correlates with a higher TNF-alpha response. |
| 714 | 8093442 | These observations suggest a direct role for the TNF locus in the pathogenesis of IDDM. |
| 715 | 8094039 | Using RFLPs at V beta 11 and V beta 8 loci TCR beta haplotypes have been identified in five families in which the probands have insulin-dependent diabetes mellitus (IDDM). |
| 716 | 8094039 | An extremely rare haplotype, marked by the higher molecular weight BamH1 allele (H, H) at each of V beta 11 and V beta 8, was found in the DR4+ DR3- probands of two families (P = 0.004). |
| 717 | 8097419 | The frequency distributions of the HLA types DR3, DR4 and DR3/4, which normally confer susceptibility to insulin-dependent diabetes mellitus and of HLA-DR2, which normally confers resistance to insulin-dependent diabetes mellitus, were not different in non-diabetic CF patients, diabetic CF patients and normal subjects. |
| 718 | 8097419 | The genotypic frequencies of tumor necrosis factor-beta and of heat shock protein 70, located within the HLA region on chromosome 6, in CF patients with diabetes were not different from those in patients with insulin-dependent diabetes mellitus, while non-diabetic CF patients and normal subjects shared other patterns. |
| 719 | 8097419 | The frequencies of the interleukin-1 beta alleles, located on chromosome 2, were not different in non-diabetic and diabetic CF patients, insulin-dependent diabetic patients and normal subjects. |
| 720 | 8157258 | Stable cell surface presentation of MHC class I molecules requires active transport of antigenic peptides across the endoplasmic reticulum by products of two genes, TAP1 and TAP2, which are maped in the MHC class II region. |
| 721 | 8157258 | The data suggests that the association of TAP2 allele with IDDM disease may be a simple reflection of the linkage disequilibrium between TAP allele and DR4 gene. |
| 722 | 8194658 | GAD antibody negative NIDDM in adult black subjects with diabetic ketoacidosis and increased frequency of human leukocyte antigen DR3 and DR4. |
| 723 | 8194658 | HLA DR3 and DR4 frequency was higher than in nondiabetic black control subjects (65 vs. 30%, P < 0.012). |
| 724 | 8194658 | GAD antibody negative NIDDM in adult black subjects with diabetic ketoacidosis and increased frequency of human leukocyte antigen DR3 and DR4. |
| 725 | 8194658 | HLA DR3 and DR4 frequency was higher than in nondiabetic black control subjects (65 vs. 30%, P < 0.012). |
| 726 | 8196846 | The relative risk (RR) was calculated using these data and its statistical significance was assessed using the chi-square test. 70.6% of subjects were positive for loci DR3 or DR4, whereas only 7.7% (11 subjects) were found to be carriers of eterozygous DR3-DR4. |
| 727 | 8196846 | The presence of antigen DQw2 is strongly indicative of the disease, both when it is found in an isolated form and in association with DR3 or DR4 (RR = 2.56, 4.03, 3.29 respectively). |
| 728 | 8196846 | The DR3/DR4/DQw2 axis gives a RR of 9.17. |
| 729 | 8196846 | The associations of B8/DR3/DR4 and B8/DR3/DQw2 give a RR of 9.17, whereas the B8/DR4 axis gives a RR of 10.47. |
| 730 | 8196846 | The relative risk (RR) was calculated using these data and its statistical significance was assessed using the chi-square test. 70.6% of subjects were positive for loci DR3 or DR4, whereas only 7.7% (11 subjects) were found to be carriers of eterozygous DR3-DR4. |
| 731 | 8196846 | The presence of antigen DQw2 is strongly indicative of the disease, both when it is found in an isolated form and in association with DR3 or DR4 (RR = 2.56, 4.03, 3.29 respectively). |
| 732 | 8196846 | The DR3/DR4/DQw2 axis gives a RR of 9.17. |
| 733 | 8196846 | The associations of B8/DR3/DR4 and B8/DR3/DQw2 give a RR of 9.17, whereas the B8/DR4 axis gives a RR of 10.47. |
| 734 | 8196846 | The relative risk (RR) was calculated using these data and its statistical significance was assessed using the chi-square test. 70.6% of subjects were positive for loci DR3 or DR4, whereas only 7.7% (11 subjects) were found to be carriers of eterozygous DR3-DR4. |
| 735 | 8196846 | The presence of antigen DQw2 is strongly indicative of the disease, both when it is found in an isolated form and in association with DR3 or DR4 (RR = 2.56, 4.03, 3.29 respectively). |
| 736 | 8196846 | The DR3/DR4/DQw2 axis gives a RR of 9.17. |
| 737 | 8196846 | The associations of B8/DR3/DR4 and B8/DR3/DQw2 give a RR of 9.17, whereas the B8/DR4 axis gives a RR of 10.47. |
| 738 | 8196846 | The relative risk (RR) was calculated using these data and its statistical significance was assessed using the chi-square test. 70.6% of subjects were positive for loci DR3 or DR4, whereas only 7.7% (11 subjects) were found to be carriers of eterozygous DR3-DR4. |
| 739 | 8196846 | The presence of antigen DQw2 is strongly indicative of the disease, both when it is found in an isolated form and in association with DR3 or DR4 (RR = 2.56, 4.03, 3.29 respectively). |
| 740 | 8196846 | The DR3/DR4/DQw2 axis gives a RR of 9.17. |
| 741 | 8196846 | The associations of B8/DR3/DR4 and B8/DR3/DQw2 give a RR of 9.17, whereas the B8/DR4 axis gives a RR of 10.47. |
| 742 | 8217479 | It has been clearly shown that type I diabetic patients more frequently display HLA DR3 and DR4 specificities. |
| 743 | 8224807 | This method has been applied to 27 DR3/DR3 parents and 50 DR4/DR4 parents who have at least 2 children affected with insulin dependent diabetes mellitus (IDDM). |
| 744 | 8224807 | The transmission of both DR3 and DR4 haplotypes is statistically different from 50% (P < 0.05 and P < 0.001, respectively). |
| 745 | 8448621 | A young woman with the HLA phenotype A1, A2, B5, B8, DR3, DR4 developed RA, idiopathic thrombocytopenic purpura (ITP), pernicious anaemia (PA), Hashimoto's thyroiditis (HT), systemic sclerosis (SS), pancreatic exocrine insufficiency (PEI) and coeliac disease (CD) before dying from vasculitic complications. |
| 746 | 8448621 | A family study revealed RA, PA and insulin-dependent diabetes mellitus (IDDM) amongst her first degree relatives. |
| 747 | 8557177 | Variation in the risk of insulin-dependent diabetes mellitus (IDDM) across alleles at HLA-A, B, and DR loci was investigated in a population-based study of 801 families of children with newly diagnosed IDDM in Finland nationwide. |
| 748 | 8557177 | The joint effects of DR3 and DR4 alleles were investigated under dominant, recessive, and additive models of gene expression. |
| 749 | 8557177 | After controlling for the correlation among alleles, significantly elevated risks were found for B13, DR3, DR4, and DR14. |
| 750 | 8557177 | Variation in the risk of insulin-dependent diabetes mellitus (IDDM) across alleles at HLA-A, B, and DR loci was investigated in a population-based study of 801 families of children with newly diagnosed IDDM in Finland nationwide. |
| 751 | 8557177 | The joint effects of DR3 and DR4 alleles were investigated under dominant, recessive, and additive models of gene expression. |
| 752 | 8557177 | After controlling for the correlation among alleles, significantly elevated risks were found for B13, DR3, DR4, and DR14. |
| 753 | 8722074 | Transcomplementation of HLA DQA1-DQB1 in DR3/DR4 and DR3/DR9 heterozygotes and IDDM in Taiwanese families. |
| 754 | 8747721 | Circulating lymphocyte subset imbalance is associated with type-1 insulin-dependent diabetes mellitus (IDDM). |
| 755 | 8747721 | Total B lymphocytes, CD19+ cells, was increased in IDDM patients (P = 0.001), but was comparable to controls in IDDM patients' first-degree relatives. |
| 756 | 8747721 | No quantitative abnormality was demonstrated in CD4+ cells in IDDM patients; however, these cells were higher in their first-degree relatives (P = 0.0089). |
| 757 | 8747721 | Suppressor T lymphocytes, CD8+ cells, in first-degree relatives and controls were not significantly different; however, these cells were significantly reduced in IDDM patients (P = 0.001). |
| 758 | 8747721 | The ratio of CD4+/CD8+ cells was higher in IDDM patients and their first-degree relatives compared to controls (P = 0.0007 and 0.0103, respectively). |
| 759 | 8747721 | However, no relationship was found in the levels of CD3+, CD4+ or CD8+ cells in patients possessing either DR3 or DR4. |
| 760 | 8875117 | Moreover, putative high responder HLA-DR1, DR3 and DR4 alleles were significantly (p < 0.001) more frequent in pre-eclampsia patients (79%) than in controls (59%). |
| 761 | 8900244 | We report here our analysis of HLA class II alleles in 180 Caucasian nuclear families with at least two children with insulin-dependent diabetes mellitus (IDDM). |
| 762 | 8900244 | DRB1, DQA1, DQB1, and DPB1 genotypes were determined with PCR/sequence-specific oligonucleotide probe typing methods. |
| 763 | 8900244 | Consistent with other studies, our data indicate an increase in DR3/DR4, DR3/DR3, and DR4/DR4 genotypes in patients compared to controls. |
| 764 | 8900244 | In addition, we found an increase in DR1/DR4, DR1/DR3, and DR4/DR8 genotypes. |
| 765 | 8900244 | We report here our analysis of HLA class II alleles in 180 Caucasian nuclear families with at least two children with insulin-dependent diabetes mellitus (IDDM). |
| 766 | 8900244 | DRB1, DQA1, DQB1, and DPB1 genotypes were determined with PCR/sequence-specific oligonucleotide probe typing methods. |
| 767 | 8900244 | Consistent with other studies, our data indicate an increase in DR3/DR4, DR3/DR3, and DR4/DR4 genotypes in patients compared to controls. |
| 768 | 8900244 | In addition, we found an increase in DR1/DR4, DR1/DR3, and DR4/DR8 genotypes. |
| 769 | 8927593 | An important factor appears to be a genetic predisposition (HLA DR3/DR4/DQ8) in connection with as yet unknown environmental factors (e.g., viruses). |
| 770 | 8927593 | Autoantibodies, such as islet cell cytoplasmic antibodies (ICA), insulin autoantibodies (IAA), and/or autoantibodies to the GABA-synthesizing enzyme glutamic acid carboxylase (GAD), are already detectable in a prediabetic phase, although it is not possible to predict the time of clinical manifestation. |
| 771 | 8943434 | Autoreactive islet cell Abs (ICA) accompany the pathogenic destruction of pancreatic beta cells in insulin-dependent diabetes mellitus (IDDM). |
| 772 | 8943434 | We have isolated 4 new ICA-reactive B cell lines, one from a DR4/DR11-positive newly diagnosed IDDM patient (MICA 7) and three from a DR3 homozygous patient with both IDDM and Graves' disease (MICA 8-10). |
| 773 | 8943434 | Like MICA 1-6, MICA 7-10 are specific for GAD65, suggesting that GAD65-reactive B cells dominate the ICA response in IDDM. |
| 774 | 8943434 | MICA 1-6, 7, and 8-10, derived from three IDDM patients of different HLA haplotypes, define six different epitopes in GAD65 and represent tools to determine the spectrum, possible HLA association, and temporal order of epitope recognition in IDDM. |
| 775 | 8948898 | The serological findings of HLA antigens showed a significant association of DR3, DR4, DQ2 and DQ8 and a protective effect of DR11, DR15, DQ5, DQ6 and DQ7. |
| 776 | 8948898 | With these results, DNA analysis of HLA-DRB1, B3, B4, DQA1, DQB1, DPA1, DPB1 genes was performed using PCR with allele specific oligotyping. |
| 777 | 8948898 | Positions 57 and 74 of DRB1 locus contribute highly to the expression and severity of IDDM in Mestizos and other ethnic groups, but not in Caucasians or Blacks. |
| 778 | 8955758 | In 15 cadaveric renal transplant patients (10 men, 5 women, ages 29-65 years) with chronic hepatitis C and histological features of chronic active hepatitis, undergoing chronic immunosuppression (ciclosporine A with or without steroid and azathioprine) and treated with recombinant alpha 2b-interferon (IFN alpha) (mean duration 142 +/- 35 days), we assessed before and after this therapy the serum levels of cryoglobulinemia, rheumatoid factors (RF), thyroid-stimulating hormone (TSH), free thyroxine (fT4), and antinuclear (ANA), antismooth muscle (ASMA), antimitochondrial (AMA), anti-LKM1, antimicrosomal thyroid (MCA), antithyroglobulin (TGA) autoantibodies. |
| 779 | 8955758 | At the start of IFN alpha therapy, 14 of 15 patients had detectable autoantibodies (RF: 9; ANA > 1/50: 8; ASMA > 1/50: 4; other autoantibodies: 0); 1 had cryoglobulinemia. |
| 780 | 8955758 | Finally, the occurrence of autoantibodies in our patients was associated either with HLA DR3 or DR4 or DR7 phenotypes. |
| 781 | 8955758 | We found that the prevalence of extrahepatic immunologic abnormalities was high in renal transplant patients with chronic hepatitis C and no exacerbation was observed during of after IFN alpha therapy. |
| 782 | 8955758 | The most frequent autoantibody appearing after IFN alpha therapy was MCA although without thyroid abnormalities. |
| 783 | 8971095 | HLA-encoded genetic predisposition in IDDM: DR4 subtypes may be associated with different degrees of protection. |
| 784 | 9015682 | We confirm for a Spanish population the high frequency of risk genotypes for Type I, involving DR3, DR4 and DQB1*0302 (DQ8) which were present in 26 of 28 (93%) patients and 32 of 41 (78%) relatives. |
| 785 | 9065059 | An important factor appears to be a genetic predisposition (HLA DR3/DR4/DQ8) in connection with as yet unknown environmental factors (e.g., viruses). |
| 786 | 9065059 | Autoantibodies, such as islet cell cytoplasmic antibodies (ICA), insulin autoantibodies (IAA) and/or autoantibodies to the GABA-synthesizing enzyme glutamic acid carboxylase (GAD), are already detectable in a prediabetic phase, though it is not possible to predict the time of clinical manifestation. |
| 787 | 9098435 | The role of HLA class II alleles in genetic predisposition to insulin-dependent diabetes mellitus (IDDM) was examined using Polymerase Chain Reaction/oligonucleotide probe typing (PCR/SSOs) of eight HLA class II loci in 58 IDDM patients and 50 healthy controls from the Northwest of Spain (Asturias). |
| 788 | 9098435 | By using the aetiologic fraction (delta) as an almost absolute measure of the strongest linkage of disequilibrium of a HLA marker to the putative Type I susceptibility locus, it has been found that the strength of association of the HLA markers may be quantified as follows: DQA1*03-DQB1*0302 or DQA1*0501-DQB1*0201 > DR3 or DR4; presence of more than one dimer DQ alpha beta of the six proposed by Rønningen > non-Asp57 DQ beta and Arg52 DQ alpha > Arg52 DQ alpha > non-Asp57 DQ beta/non-Asp57 DQ beta > DRB1*0301; DQA1*0501-DQB1*0201 > DQA1*03-DQB1*0302; DQB1*0302. |
| 789 | 9098450 | Application of the relative predispositional effect (RPE) method to our data, revealed a further susceptibility risk provided by the DRB1*13-DQA1*0102-DQB1*0604 haplotype once DR3 and DR4 haplotypes were removed. |
| 790 | 9201596 | The aim of this study was to evaluate the role of HLA (human leucocyte antigen) class I (A, B, C) and class II (DR) alleles and familial insulin-dependent diabetes mellitus as possible risk markers for early retinopathy in a population of 103 Finnish adolescents with type I diabetes mellitus for 3.6-16.2 years. |
| 791 | 9201596 | The frequency of HLA DR3, DR4, or DR3/4 heterozygosity did not differ between the two groups of patients. |
| 792 | 9239904 | The role of HLA class II alleles in the genetic susceptibility to develop insulin-dependent diabetes mellitus (IDDM) was examined by means of PCR and oligospecific probes in 63 IDDM children and 74 controls subjects. |
| 793 | 9239904 | In diabetic patients we found a significant increase in the alleles frequency DR3, DR4, DQB1*0302 and DQA1*0301 compared to the control group, where the most prevalent alleles were DR2, DR14 (DRB1*1402), DQA1*0101 and DQA1*0201. |
| 794 | 9254534 | At the present time, there are markers which we can use to identify individuals with a high susceptibility of developing insulin-dependent diabetes mellitus (IDDM) years before the onset of the disease. |
| 795 | 9254534 | Insulin-dependent diabetes mellitus is an autoimmune disease strongly associated with HLA antigens DR3 and DR4. |
| 796 | 9254534 | In this manuscript, we discuss the usefulness of several markers, such as islet cell antibodies, insulin autoantibodies and glutamic acid decarboxylase antibodies, to identify individuals with a high susceptibility to IDDM before the disease is clinically evident. |
| 797 | 9254534 | Currently, two large-scale multicentric human trials, one in Europe using nicotinamide (European Nicotinamide Diabetes Intervention Trial, ENDIT) and the other in the USA using insulin (Diabetes Prevention Trial), are now in full activity and will test the benefits of these drugs in the prophylaxis of IDDM in highly susceptible individuals. |
| 798 | 9353155 | CTLA-4 gene polymorphism confers susceptibility to insulin-dependent diabetes mellitus (IDDM) independently from age and from other genetic or immune disease markers. |
| 799 | 9353155 | Apart from genes in the HLA complex (IDDM1) and the variable number of tandem repeats in the 5' region of the insulin gene (INS VNTR, IDDM2), several other loci have been proposed to contribute to IDDM susceptibility. |
| 800 | 9353155 | Recently, linkage and association have been shown between the cytotoxic T lymphocyte-associated protein 4 (CTLA-4) gene on chromosome 2q and IDDM. |
| 801 | 9353155 | In a registry-based group of 525 recent-onset IDDM patients <40 years old we investigated the possible interactions of a CTLA-4 gene A-to-G transition polymorphism with age at clinical disease onset and with the presence or absence of established genetic (HLA-DQ, INS VNTR) and immune disease markers (autoantibodies against islet cell cytoplasm (ICA); insulin (IAA); glutamate decarboxylase (GAD65-Ab); IA-2 protein tyrosine phosphatase (IA-2-Ab)) determined within the first week of insulin treatment. |
| 802 | 9353155 | G-allele-containing CTLA-4 genotypes (relative risk (RR)= 1.5; 95% confidence interval (CI) = 1.2-2.0; P < 0.005) were not preferentially associated with age at clinical presentation or with the presence of other genetic (HLA-DR3 or DR4 alleles; HLA-DQA1*0301-DQB1*0302 and/or DQA1*0501-DQB1*0201 risk haplotypes; INS VNTR I/I risk genotype) or immune (ICA, IAA, IA-2-Ab, GAD65-Ab) markers of diabetes. |
| 803 | 9353155 | For 151 patients, thyrogastric autoantibodies (anti-thyroid peroxidase, anti-thyroid-stimulating hormone (TSH) receptor, anti-parietal cell, anti-intrinsic factor) were determined, but association between CTLA-4 risk genotypes and markers of polyendocrine autoimmunity could not be demonstrated before or after stratification for HLA- or INS-linked risk. |
| 804 | 9353155 | In conclusion, the presence of a G-containing CTLA-4 genotype confers a moderate but significant RR for IDDM that is independent of age and genetic or immune disease markers. |
| 805 | 9405979 | Persistent GAD 65 antibodies in longstanding IDDM are not associated with residual beta-cell function, neuropathy or HLA-DR status. |
| 806 | 9405979 | Persistent humoral autoimmunity to the enzyme glutamic acid decarboxylase (GAD) has been described in a substantial proportion of patients with insulin-dependent diabetes mellitus (IDDM) of long duration. |
| 807 | 9405979 | Because the GAD 65 isoform is mainly expressed in pancreatic beta-cells and in the nervous system we investigated in the present study of the largest number of well characterized patients with longstanding IDDM (n = 105; median duration: 21 years; range: 10-46 years) the presence of autoantibodies to GAD 65 and their relationship to a residual C-peptide response or peripheral and autonomic neuropathy. |
| 808 | 9405979 | One hundred healthy control subjects and 100 recent onset IDDM patients were also studied for GAD 65 antibodies. |
| 809 | 9405979 | GAD 65 antibodies were detected in a radioligand-binding-assay with recombinant human GAD 65 and were present in 32% of the long-term diabetic patients, 82% of the recent onset IDDM patients and in 3% of the healthy control subjects. |
| 810 | 9405979 | Patients who were heterozygous for DR3/DR4 were found in 23% of the cases. |
| 811 | 9405979 | GAD 65 antibodies were significantly less frequent in the long-term IDDM patients compared to recent onset IDDM (p < 0.001), and diabetes duration showed a significant negative correlation with GAD 65 antibody index levels (r = 0.22, p < 0.01). |
| 812 | 9405979 | In conclusion neither residual beta-cell function nor diabetic neuropathy or a certain HLA-DR specificity are exclusively associated with persistent autoimmunity directed to GAD 65 in longstanding IDDM. |
| 813 | 9438201 | Five to 20% insulin-dependent diabetes mellitus (IDDM) patients do not bear the classical HLA class II DR3 or DR4 susceptibility haplotypes. |
| 814 | 9498628 | It has been proposed that molecular mimicry between protein 2C (p2C) of coxsackie virus B4 and the autoantigen glutamic acid decarboxylase (GAD65) plays a role in the pathogenesis of insulin-dependent diabetes mellitus (IDDM). |
| 815 | 9498628 | Therefore, we tested whether the PEVKEK motif can bind to the IDDM-associated HLA-DR1, -DR3 and -DR4 molecules. |
| 816 | 9704223 | Similar frequencies of HLA-DR2, DR3, and DR4 antigens in healthy pregnant women and women with GDM and low prevalences of markers for autoimmune destruction of the beta-cells in GDM pregnancy rule out the possibility that GDM is a disease of autoimmune origin. |
| 817 | 9704223 | Insulin receptor binding to target tissues is largely unaffected by normal and GDM pregnancy; the same is true for basal and insulin-stimulated insulin receptor-bound tyrosine kinase activity. |
| 818 | 9704223 | Hormones that circulate in high concentrations in pregnancy (e.g., progesterone, cortisol, prolactin, human placental lactogen, and estrogen) have all been shown, in animal models, to be able to influence beta-cell function and/or the peripheral tissue sensitivity to insulin, but whether they play similar roles in human pregnancy remains to be investigated. |
| 819 | 9827157 | In insulin-dependent diabetes mellitus, HLA-DR markers are involved, namely DR3, DR4 and DR9 alleles, among black senegalese populations. |
| 820 | 9828917 | Autoimmune IDDM in a sporadic MELAS patient with mitochondrial tRNA(Leu(UUR)) mutation. |
| 821 | 9828917 | He was also affected with insulin-dependent diabetes mellitus (IDDM), as diagnosed by the experience of diabetic ketoacidosis (DKA), and dependence on insulin therapy. |
| 822 | 9828917 | In addition, human leucocyte associated antigen (HLA) typing showed DR3 and DR4, suggesting the strong contribution of autoimmunity to the pathogenesis of IDDM in this patient. |
| 823 | 9828917 | This extremely rare case of sporadic MELAS syndrome with autoimmune IDDM harbouring mtDNA mutation highlights the possible pathogenetic role of mtDNA mutations in autoimmune disease. |
| 824 | 9867222 | Mutations in the hepatocyte nuclear factor-1alpha (HNF-1alpha) gene are the cause of maturity-onset diabetes of the young type 3 (MODY3), which is characterised by a severe impairment of insulin secretion and an early onset of the disease. |
| 825 | 9867222 | Also at onset of diabetes some MODY patients show similar clinical symptoms and signs as patients with Type I (insulin-dependent) diabetes mellitus. |
| 826 | 9867222 | DR3 or DR4 or both were examined by single-strand conformational polymorphism scanning and direct sequencing of the coding region and the minimal promoter of the HNF-1alpha gene. |
| 827 | 10197051 | Blockade of this presentation event via synthetic ligands that bind to disease-associated MHCs (such as DR1 and DR4) may be useful for the treatment of autoimmune diseases such as rheumatoid arthritis, Type 1 diabetes, multiple sclerosis, lupus erthymatosis and Graves disease. |
| 828 | 10197051 | Recently reported synthetic ligands for DR1 and DR4 are short modified peptides (2-7 mers) capable of competing at nanomolar concentrations with antigenic peptides for the DR (MHC) binding groove. |
| 829 | 10197051 | Blockade of this presentation event via synthetic ligands that bind to disease-associated MHCs (such as DR1 and DR4) may be useful for the treatment of autoimmune diseases such as rheumatoid arthritis, Type 1 diabetes, multiple sclerosis, lupus erthymatosis and Graves disease. |
| 830 | 10197051 | Recently reported synthetic ligands for DR1 and DR4 are short modified peptides (2-7 mers) capable of competing at nanomolar concentrations with antigenic peptides for the DR (MHC) binding groove. |
| 831 | 10404800 | Predictive value of human leukocyte antigen class II typing for the development of islet autoantibodies and insulin-dependent diabetes postpartum in women with gestational diabetes. |
| 832 | 10404800 | Gestational diabetes mellitus (GDM) is a risk factor for the development of insulin-dependent diabetes mellitus (IDDM) and noninsulin-dependent diabetes mellitus postpartum. |
| 833 | 10404800 | To evaluate whether there is any association of human leukocyte antigen (HLA) class II alleles (DR and DQ) with GDM and the postpartum development of IDDM, we analyzed 184 women with GDM from Germany for HLA class II alleles, islet autoantibodies [islet cell autoantibodies (ICA), glutamic acid decarboxylase autoantibodies (GADA), and protein tyrosine phosphatase IA-2 autoantibodies (IA-2A), and the postpartum development of diabetes. |
| 834 | 10404800 | Twenty-five (59.5%) islet antibody-positive women and 17 (74%) women who developed IDDM postpartum had a DR3- or DR4-containing genotype. |
| 835 | 10404800 | The cumulative risk to develop IDDM within 2 yr postpartum in GDM women with either DR3 or DR4 was 22% compared to 7% in women without those alleles (P = 0.02) and rose to 50% in the DR3- or DR4-positive women who had required insulin during pregnancy (P = 0.006). |
| 836 | 10404800 | Combining the determination of susceptible HLA alleles (DR3, DR4) with islet autoantibody measurement increased the sensitivity of identifying GDM women developing postpartum IDDM to 92%, but did not improve risk assessment above that achieved using GADA measurement alone, which was the strongest predictor of IDDM. |
| 837 | 10404800 | Predictive value of human leukocyte antigen class II typing for the development of islet autoantibodies and insulin-dependent diabetes postpartum in women with gestational diabetes. |
| 838 | 10404800 | Gestational diabetes mellitus (GDM) is a risk factor for the development of insulin-dependent diabetes mellitus (IDDM) and noninsulin-dependent diabetes mellitus postpartum. |
| 839 | 10404800 | To evaluate whether there is any association of human leukocyte antigen (HLA) class II alleles (DR and DQ) with GDM and the postpartum development of IDDM, we analyzed 184 women with GDM from Germany for HLA class II alleles, islet autoantibodies [islet cell autoantibodies (ICA), glutamic acid decarboxylase autoantibodies (GADA), and protein tyrosine phosphatase IA-2 autoantibodies (IA-2A), and the postpartum development of diabetes. |
| 840 | 10404800 | Twenty-five (59.5%) islet antibody-positive women and 17 (74%) women who developed IDDM postpartum had a DR3- or DR4-containing genotype. |
| 841 | 10404800 | The cumulative risk to develop IDDM within 2 yr postpartum in GDM women with either DR3 or DR4 was 22% compared to 7% in women without those alleles (P = 0.02) and rose to 50% in the DR3- or DR4-positive women who had required insulin during pregnancy (P = 0.006). |
| 842 | 10404800 | Combining the determination of susceptible HLA alleles (DR3, DR4) with islet autoantibody measurement increased the sensitivity of identifying GDM women developing postpartum IDDM to 92%, but did not improve risk assessment above that achieved using GADA measurement alone, which was the strongest predictor of IDDM. |
| 843 | 10404800 | Predictive value of human leukocyte antigen class II typing for the development of islet autoantibodies and insulin-dependent diabetes postpartum in women with gestational diabetes. |
| 844 | 10404800 | Gestational diabetes mellitus (GDM) is a risk factor for the development of insulin-dependent diabetes mellitus (IDDM) and noninsulin-dependent diabetes mellitus postpartum. |
| 845 | 10404800 | To evaluate whether there is any association of human leukocyte antigen (HLA) class II alleles (DR and DQ) with GDM and the postpartum development of IDDM, we analyzed 184 women with GDM from Germany for HLA class II alleles, islet autoantibodies [islet cell autoantibodies (ICA), glutamic acid decarboxylase autoantibodies (GADA), and protein tyrosine phosphatase IA-2 autoantibodies (IA-2A), and the postpartum development of diabetes. |
| 846 | 10404800 | Twenty-five (59.5%) islet antibody-positive women and 17 (74%) women who developed IDDM postpartum had a DR3- or DR4-containing genotype. |
| 847 | 10404800 | The cumulative risk to develop IDDM within 2 yr postpartum in GDM women with either DR3 or DR4 was 22% compared to 7% in women without those alleles (P = 0.02) and rose to 50% in the DR3- or DR4-positive women who had required insulin during pregnancy (P = 0.006). |
| 848 | 10404800 | Combining the determination of susceptible HLA alleles (DR3, DR4) with islet autoantibody measurement increased the sensitivity of identifying GDM women developing postpartum IDDM to 92%, but did not improve risk assessment above that achieved using GADA measurement alone, which was the strongest predictor of IDDM. |
| 849 | 10426387 | The strongest associations were found with the A locus: DR3/DR4 genotype frequency decreases with age of onset in this data set only among A*0101- individuals, and A*2402 is strongly associated with younger age of onset in many DR-DQ haplotypes. |
| 850 | 10714434 | The analysis of in vitro transforming growth factor-beta1 (TGF-beta1) production by peripheral blood in overt and pre-clinical type 1 diabetes mellitus. |
| 851 | 10714434 | The alterations of TGF-beta1 production are believed to contribute to the development of insulin-dependent diabetes mellitus (IDDM) in animal models as well as in humans. |
| 852 | 10714434 | The aim of our study was to evaluate in vitro TGF-beta1 production by peripheral blood of newly diagnosed type 1 diabetes patients and subjects in the pre-clinical stage of the disease in comparison to healthy controls and relatives of IDDM patients with low genetic risk for diabetes development. |
| 853 | 10714434 | In the first degree relatives HLA typing (for DR3, DR4 and DQB1*0602 alleles), measurements of anti-pancreatic antibodies (ICA, GADA, IA-2A, IAA) and intravenous glucose tolerance tests were performed. |
| 854 | 10714434 | In the group of first degree relatives TGF-beta1 levels were highest in subjects with the presence of two or more pancreatic autoantibodies and/or with impaired insulin release in IVGTT, but lowest in relatives with protective DQB1*0602 alleles (P < 0.01). |
| 855 | 10714434 | There was also a significant positive correlation between the TGF-beta1 levels and HbA1C in the IDDM subjects and first degree relatives (P < 0.03). |
| 856 | 10725774 | Thyroid autoimmunity tended to be more prevalent in the subgroup of patients with the HLA type DR3/DR4 compared to patients with other HLA types (p = 0.08). |
| 857 | 10871191 | HLA DQ8 and DQ2 have been shown to strongly predispose to disease and to be in linkage disequilibrium with at-risk DR4 and DR3 alleles, respectively. |
| 858 | 10871191 | Inheritance of a mixed DR3/DR4 haplotype confers the greatest risk. |
| 859 | 10871191 | HLA DQ8 and DQ2 have been shown to strongly predispose to disease and to be in linkage disequilibrium with at-risk DR4 and DR3 alleles, respectively. |
| 860 | 10871191 | Inheritance of a mixed DR3/DR4 haplotype confers the greatest risk. |
| 861 | 11024583 | Some environmental and genetic factors play important roles in etiopathogenesis of type 1 or insulin-dependent diabetes mellitus (IDDM). |
| 862 | 11024583 | HLA genes, the IDDM1 locus located the human chromosome 6, were found to be associated with insulin-dependent diabetes mellitus. |
| 863 | 11024583 | To study detailed molecular structure of class II HLA molecules and disease association, we examined several amino acid residues on DQalpha and DQbeta chains and the molecular mechanisms to explain the heterozygotic effect of the DR3/DR4 and DR3/DR9 in the Chinese population. |
| 864 | 11024583 | Among the several class II alleles, a closer segregation of HLA-DQB1*0401 to the affected persons might suggest that HLA-DQB1*0401 itself or an allele closely linked to the DQB1 locus was the IDDM-predisposing allele in Taiwanese. |
| 865 | 11024583 | For IDDM2 (INS) region, association with IDDM was not found due to that more than 90% of the population carried class I alleles. |
| 866 | 11221543 | Our results revealed that the frequencies of DR3, DR4 and DR9 in diabetes patients were significantly higher than those in control group (all P < 0.01). |
| 867 | 11221543 | The susceptible alleles were DR3, DR4, DR9, with relative risks of 8.25, 2.57 and 2.67, respectively. |
| 868 | 11221543 | There was a trend that the frequencies of DR9 decreased with the increase of age at onset, but there was no significant difference of DR3, DR4, DR9, DR3/4, DR3/9 and DR4/9 frequencies between diabetes children with age onset 0-10 years and 11-17 years. |
| 869 | 11221543 | Our results revealed that the frequencies of DR3, DR4 and DR9 in diabetes patients were significantly higher than those in control group (all P < 0.01). |
| 870 | 11221543 | The susceptible alleles were DR3, DR4, DR9, with relative risks of 8.25, 2.57 and 2.67, respectively. |
| 871 | 11221543 | There was a trend that the frequencies of DR9 decreased with the increase of age at onset, but there was no significant difference of DR3, DR4, DR9, DR3/4, DR3/9 and DR4/9 frequencies between diabetes children with age onset 0-10 years and 11-17 years. |
| 872 | 11221543 | Our results revealed that the frequencies of DR3, DR4 and DR9 in diabetes patients were significantly higher than those in control group (all P < 0.01). |
| 873 | 11221543 | The susceptible alleles were DR3, DR4, DR9, with relative risks of 8.25, 2.57 and 2.67, respectively. |
| 874 | 11221543 | There was a trend that the frequencies of DR9 decreased with the increase of age at onset, but there was no significant difference of DR3, DR4, DR9, DR3/4, DR3/9 and DR4/9 frequencies between diabetes children with age onset 0-10 years and 11-17 years. |
| 875 | 11269900 | He expresses the alleles DQ2 A1 0501 and B1 which are strongly associated with susceptibility to insulin-dependent diabetes mellitus and celiac disease, but don't express antigens HLA class II DR3 and DR4 that are more frequent in these entities. |
| 876 | 11532327 | Higher prevalence of GAD antibody in diabetes patients using a new radioligand-binding assay with recombinant human GAD65 antibodies (GAD65Ab) has been seen in several studies. |
| 877 | 11532327 | There was no significant difference in gender, diabetes onset and duration, HbA1c, C-peptide concentration and frequencies of HLA DR3, DR4, DR9, DR3/DR4, DR3/DR9 and DR4/DR9 genotypes between GAD65Ab+ and GAD65Ab- groups. |
| 878 | 11532327 | The frequencies of antimicrosomal and anti-thyroglobulin antibodies in GAD65Ab+ (13.5,8.1%, respectively) were not different from GAD65- patients (9.4,12.5%, respectively). |
| 879 | 11668578 | Both groups of probands have almost identical frequencies of DR and DQ haplotypes but significantly different IBD distributions in the subset of families with probands who do not carry the highly predisposing DR3/DR4 genotype. |
| 880 | 11668578 | Our results are consistent with previous reports implicating DPB1 in IDDM susceptibility. |
| 881 | 11679444 | To study the dynamics of disease-associated humoral immune responses, we analyzed autoantibodies to the IA-2 protein (IA-2A), glutamic acid decarboxylase (GADA), and insulin (IAA) and also islet cell antibodies (ICA) in a population-based, prospective, representative series of 710 siblings (<20 years of age) of children with type 1 diabetes. |
| 882 | 11679444 | Positive seroconversions seemed to be associated with a young age of the sibling, HLA DR3/DR4 heterozygosity, HLA identity, and a high initial number of detectable autoantibodies. |
| 883 | 11679444 | No consistent risk factor for inverse seroconversions was present, although seroconversions were most frequent in siblings with older age, male sex, HLA phenotypes other than DR3/DR4, a small family size, and no other autoantibodies detectable at seroconversion. |
| 884 | 11679444 | To study the dynamics of disease-associated humoral immune responses, we analyzed autoantibodies to the IA-2 protein (IA-2A), glutamic acid decarboxylase (GADA), and insulin (IAA) and also islet cell antibodies (ICA) in a population-based, prospective, representative series of 710 siblings (<20 years of age) of children with type 1 diabetes. |
| 885 | 11679444 | Positive seroconversions seemed to be associated with a young age of the sibling, HLA DR3/DR4 heterozygosity, HLA identity, and a high initial number of detectable autoantibodies. |
| 886 | 11679444 | No consistent risk factor for inverse seroconversions was present, although seroconversions were most frequent in siblings with older age, male sex, HLA phenotypes other than DR3/DR4, a small family size, and no other autoantibodies detectable at seroconversion. |
| 887 | 11770176 | The occurrence of the haplotypes HLA DQ2/DR3 and/or DQ8/DR4 was observed in two thirds of type 1 diabetic and LADA patients. |
| 888 | 12021131 | Among 3756 newborns born in southeast Sweden we have found the high-risk genotype DQ2/DR3-DO8/DR4 to be present in 1%, haplotype DQ8/DR4 in 7.8%, and haplotype DQ2/DR3 in 9.6%. |
| 889 | 12021131 | DQ2/DR3 or DQ8/DR4 was carried by 16.4% of newborns; the low-risk DQ6 molecule was carried by newborns as follows: DQ2/DR3-DQ6/DR15, 1.3%; DQ8/DR4-DQ6/DR15, 1.3%; and DQ6/DR15, 9.4%. |
| 890 | 12021131 | Among 3756 newborns born in southeast Sweden we have found the high-risk genotype DQ2/DR3-DO8/DR4 to be present in 1%, haplotype DQ8/DR4 in 7.8%, and haplotype DQ2/DR3 in 9.6%. |
| 891 | 12021131 | DQ2/DR3 or DQ8/DR4 was carried by 16.4% of newborns; the low-risk DQ6 molecule was carried by newborns as follows: DQ2/DR3-DQ6/DR15, 1.3%; DQ8/DR4-DQ6/DR15, 1.3%; and DQ6/DR15, 9.4%. |
| 892 | 12021135 | Associations of HLA-DR3/DQ2 with GAD65 and DR4 with IA-2 antibodies in insulin-dependent diabetes mellitus (IDDM) and DR3/DQ2 with GAD65 antibodies in latent autoimmune diabetes in adult (LADA) patients are known. |
| 893 | 12021135 | The aim of the present study was to look for association of HLA DR and DQ with GAD65, IA2 and ICA12 antibodies in IDDM (n = 97), LADA (n = 32), and malnutrition-modulated diabetes mellitus (MMDM) (n = 22) patients from northern India. |
| 894 | 12021135 | Antibodies to GAD65, IA-2, and ICA-12 were assayed by radioimmunoassay using (35)S-labeled recombinant human GAD65, IA2, and ICA12 using the in vitro transcription-translation method. |
| 895 | 12021135 | We found DR3 (29% vs. 11%) and DQ2 (36% vs. 14%) were increased in GAD65 antibody-positive compared to GAD65 antibody-negative IDDM patients (P > 0.05). |
| 896 | 12021135 | ICA 12 antibodies were increased in either DR3 or DR4 (84% vs. 69%) positives compared to non-DR3/DR4 IDDM patients (P > 0.05). |
| 897 | 12021135 | However in LADA patients, ICA12 was increased in non-DR3/DR4 patients compared to DR3- or DR4-positive patients (P < 0.05). |
| 898 | 12021135 | Associations of HLA-DR3/DQ2 with GAD65 and DR4 with IA-2 antibodies in insulin-dependent diabetes mellitus (IDDM) and DR3/DQ2 with GAD65 antibodies in latent autoimmune diabetes in adult (LADA) patients are known. |
| 899 | 12021135 | The aim of the present study was to look for association of HLA DR and DQ with GAD65, IA2 and ICA12 antibodies in IDDM (n = 97), LADA (n = 32), and malnutrition-modulated diabetes mellitus (MMDM) (n = 22) patients from northern India. |
| 900 | 12021135 | Antibodies to GAD65, IA-2, and ICA-12 were assayed by radioimmunoassay using (35)S-labeled recombinant human GAD65, IA2, and ICA12 using the in vitro transcription-translation method. |
| 901 | 12021135 | We found DR3 (29% vs. 11%) and DQ2 (36% vs. 14%) were increased in GAD65 antibody-positive compared to GAD65 antibody-negative IDDM patients (P > 0.05). |
| 902 | 12021135 | ICA 12 antibodies were increased in either DR3 or DR4 (84% vs. 69%) positives compared to non-DR3/DR4 IDDM patients (P > 0.05). |
| 903 | 12021135 | However in LADA patients, ICA12 was increased in non-DR3/DR4 patients compared to DR3- or DR4-positive patients (P < 0.05). |
| 904 | 12021135 | Associations of HLA-DR3/DQ2 with GAD65 and DR4 with IA-2 antibodies in insulin-dependent diabetes mellitus (IDDM) and DR3/DQ2 with GAD65 antibodies in latent autoimmune diabetes in adult (LADA) patients are known. |
| 905 | 12021135 | The aim of the present study was to look for association of HLA DR and DQ with GAD65, IA2 and ICA12 antibodies in IDDM (n = 97), LADA (n = 32), and malnutrition-modulated diabetes mellitus (MMDM) (n = 22) patients from northern India. |
| 906 | 12021135 | Antibodies to GAD65, IA-2, and ICA-12 were assayed by radioimmunoassay using (35)S-labeled recombinant human GAD65, IA2, and ICA12 using the in vitro transcription-translation method. |
| 907 | 12021135 | We found DR3 (29% vs. 11%) and DQ2 (36% vs. 14%) were increased in GAD65 antibody-positive compared to GAD65 antibody-negative IDDM patients (P > 0.05). |
| 908 | 12021135 | ICA 12 antibodies were increased in either DR3 or DR4 (84% vs. 69%) positives compared to non-DR3/DR4 IDDM patients (P > 0.05). |
| 909 | 12021135 | However in LADA patients, ICA12 was increased in non-DR3/DR4 patients compared to DR3- or DR4-positive patients (P < 0.05). |
| 910 | 12021139 | Patients with type 1 diabetes had significantly higher frequency of DR3, DQ2, DR4, and DQ8 alleles when compared to healthy controls. |
| 911 | 12021139 | No significant difference was observed in frequency of DR3 between ABO blood group incompatibility and type 1 diabetes patients. |
| 912 | 12021140 | Microsatellite allele 5 of MHC class I chain-related gene a increases the risk for insulin-dependent diabetes mellitus in latvians. |
| 913 | 12021140 | Insulin-dependent diabetes mellitus (IDDM) is one of the most common chronic diseases. |
| 914 | 12021140 | HLA-DQ8/DR4 and DQ2/DR3 are positively associated with IDDM and DQ6 is negatively associated with IDDM in most Caucasian populations. |
| 915 | 12021140 | The MICA gene is located in the MHC class I region and is expressed by monocytes, keratinocytes, and endothelial cells. |
| 916 | 12021140 | Analysis of allele distribution among 93 Latvian IDDM patients and 108 healthy controls showed that allele A5 of MICA is significantly increased in IDDM patients [33/93 (35%)] compared to healthy controls [22/108 (20%)] (OR = 2.15; P = 0.016). |
| 917 | 12021140 | In conclusion, we believe that MICA may play an important role in the etiopathogenesis of IDDM. |
| 918 | 12021142 | Tumor necrosis factor-alpha allele 2 shows an association with insulin-dependent diabetes mellitus in Latvians. |
| 919 | 12021142 | Insulin-dependent diabetes mellitus (IDDM) is one of the most common chronic diseases. |
| 920 | 12021142 | Genes contributing the most for development of IDDM are located on chromosome 6p21.3 in the region called the major histocompatibility complex (MHC). |
| 921 | 12021142 | HLA-DQ8/DR4 and DQ2/DR3 have shown positive association with IDDM, while DQ6 has negative association with IDDM in most Caucasian populations. |
| 922 | 12021142 | The location of the tumor necrosis factor alpha (TNF-alpha) gene in the MHC suggests the role of TNF in the etiology of IDDM as an autoimmune disease. |
| 923 | 12021142 | Ninety-two Latvian IDDM patients corresponding to WHO diagnostic criteria and 107 unrelated age- and sex-matched healthy controls were analyzed for the frequency of TNF-alpha alleles to test the hypothesis that TNF-alpha is associated with IDDM. |
| 924 | 12021142 | We found that TNF-alpha microsatellite allele 2 is associated with IDDM, 29/92 (32%), versus 14/107 (13%) in healthy controls. |
| 925 | 12021142 | The test of the strongest association of the MICA A5 allele and TNF-alpha allele 2 with IDDM showed that both are independently associated with the disease. |
| 926 | 12114788 | An important factor appears to be a genetic predisposition (human leukocyte antigen [HLA] DR3/DR4/DQ8) in connection with as-yet-unknown environmental factors (e.g., viruses). |
| 927 | 12114788 | Autoantibodies, such as islet cell cytoplasmic antibodies (ICA). insulin autoantibodies (IAA) and/or autoantibodies to the gamma-aminobutyric acid (GABA)-synthesizing enzyme glutamic acid carboxylase (GAD), are already detectable in a prediabetic phase, though it is not possible to predict the time of clinical onset. |
| 928 | 12392510 | Intra-MHC sequences including MHC class I chain-related genes (MICAs), D6S273 and D6S2223 are associated with autoimmune diseases in addition to HLA class II. |
| 929 | 12392510 | The MICA-A5.1 allele was increased on both the DR3 and DR4 haplotypes, independent of DQ and DRB1 subtyping, in the patients with Addison's disease compared with the controls. |
| 930 | 12401728 | IL4R encodes a subunit of the interleukin-4 receptor, a molecule critical to T-helper cell development. |
| 931 | 12401728 | In particular, we have identified a specific haplotype that appears to be protective and observed that this protective effect is strongest among individuals not carrying the HLA DR3/DR4 genotype (which confers the strongest genetic risk for type 1 diabetes). |
| 932 | 12632104 | Like the Fas/Fas-L system, the tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL) transduces apoptosis in a number of cancers; it is also a clinical candidate for cancer therapy. |
| 933 | 12632104 | Caspase-3 activity and the expression of four types of TRAIL receptor mRNAs were quantitated in tumor and contiguous non-tumor tissues obtained from 27 patients with HCC (HBV-related in 10; HCV-related in 17). |
| 934 | 12632104 | The expression of caspase-3 and TRAIL receptors was also examined immunohistochemically. |
| 935 | 12632104 | A significantly positive correlation was observed between caspase-3 activity and TRAIL-R1, -R2. |
| 936 | 12632104 | Caspase-3 activity and TRAIL-R1, -R2 expression in tumor tissue were significantly lower than those in non-tumor tissue in HBV-related HCC. |
| 937 | 12632104 | Some HCV-related HCC cases, however, demonstrated elevated caspase-3 activity and TRAIL-R1, -R2 expression in tumor tissue. |
| 938 | 12632104 | Both TRAIL-R1 and -R2 showed coefficient correlation with caspase-3 activity, and were strongly associated with apoptosis in human HCC. |
| 939 | 12632104 | Like the Fas/Fas-L system, the tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL) transduces apoptosis in a number of cancers; it is also a clinical candidate for cancer therapy. |
| 940 | 12632104 | Caspase-3 activity and the expression of four types of TRAIL receptor mRNAs were quantitated in tumor and contiguous non-tumor tissues obtained from 27 patients with HCC (HBV-related in 10; HCV-related in 17). |
| 941 | 12632104 | The expression of caspase-3 and TRAIL receptors was also examined immunohistochemically. |
| 942 | 12632104 | A significantly positive correlation was observed between caspase-3 activity and TRAIL-R1, -R2. |
| 943 | 12632104 | Caspase-3 activity and TRAIL-R1, -R2 expression in tumor tissue were significantly lower than those in non-tumor tissue in HBV-related HCC. |
| 944 | 12632104 | Some HCV-related HCC cases, however, demonstrated elevated caspase-3 activity and TRAIL-R1, -R2 expression in tumor tissue. |
| 945 | 12632104 | Both TRAIL-R1 and -R2 showed coefficient correlation with caspase-3 activity, and were strongly associated with apoptosis in human HCC. |
| 946 | 12632104 | Like the Fas/Fas-L system, the tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL) transduces apoptosis in a number of cancers; it is also a clinical candidate for cancer therapy. |
| 947 | 12632104 | Caspase-3 activity and the expression of four types of TRAIL receptor mRNAs were quantitated in tumor and contiguous non-tumor tissues obtained from 27 patients with HCC (HBV-related in 10; HCV-related in 17). |
| 948 | 12632104 | The expression of caspase-3 and TRAIL receptors was also examined immunohistochemically. |
| 949 | 12632104 | A significantly positive correlation was observed between caspase-3 activity and TRAIL-R1, -R2. |
| 950 | 12632104 | Caspase-3 activity and TRAIL-R1, -R2 expression in tumor tissue were significantly lower than those in non-tumor tissue in HBV-related HCC. |
| 951 | 12632104 | Some HCV-related HCC cases, however, demonstrated elevated caspase-3 activity and TRAIL-R1, -R2 expression in tumor tissue. |
| 952 | 12632104 | Both TRAIL-R1 and -R2 showed coefficient correlation with caspase-3 activity, and were strongly associated with apoptosis in human HCC. |
| 953 | 12632104 | Like the Fas/Fas-L system, the tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL) transduces apoptosis in a number of cancers; it is also a clinical candidate for cancer therapy. |
| 954 | 12632104 | Caspase-3 activity and the expression of four types of TRAIL receptor mRNAs were quantitated in tumor and contiguous non-tumor tissues obtained from 27 patients with HCC (HBV-related in 10; HCV-related in 17). |
| 955 | 12632104 | The expression of caspase-3 and TRAIL receptors was also examined immunohistochemically. |
| 956 | 12632104 | A significantly positive correlation was observed between caspase-3 activity and TRAIL-R1, -R2. |
| 957 | 12632104 | Caspase-3 activity and TRAIL-R1, -R2 expression in tumor tissue were significantly lower than those in non-tumor tissue in HBV-related HCC. |
| 958 | 12632104 | Some HCV-related HCC cases, however, demonstrated elevated caspase-3 activity and TRAIL-R1, -R2 expression in tumor tissue. |
| 959 | 12632104 | Both TRAIL-R1 and -R2 showed coefficient correlation with caspase-3 activity, and were strongly associated with apoptosis in human HCC. |
| 960 | 12691706 | Major histocompatibility complex (MHC) class I chain related gene-A (MIC-A) is associated with type 1 diabetes mellitus (T1DM) in other populations. |
| 961 | 12691706 | MIC-A6 conferred protection (OR = 0.098, p(c) = 0.032) in females heterozygous for DR3/DR4. |
| 962 | 12706109 | Of these 10 SNPs, 5 are located between DQB1 and DRB1, confirming the known association with the DR3 and DR4 haplotypes whereas two additional SNPs also reproduced known associations of T1D with DOB and LTA. |
| 963 | 12706109 | In the CD pool also, two earlier described associations were found with SNPs close to DRB1 and MICA. |
| 964 | 12706864 | Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) has been shown to exert potent cytotoxic activity against many tumor cells but not normal cells. |
| 965 | 12706864 | We found that most TRAIL-resistant and -partial resistant clones expressed low levels of DR5, whereas most TRAIL-sensitive clones expressed high levels of Death Receptor (DR5). |
| 966 | 12706864 | However, there were clones with a range of different TRAIL-sensitivities that had similar levels of DR5 expression. |
| 967 | 12706864 | The expression levels of DR4 and the decoy receptors, DcR1 and DcR2, did not correlate with TRAIL sensitivities. |
| 968 | 12706864 | We also compared the subgroups in terms of the expression of Fas-associated death domain protein (FADD), the levels of activation of Receptor Interacting Protein (RIP) and caspases, and cleavage of Poly (ADP-Ribose)Polymerase (PARP). |
| 969 | 12706864 | After treatment with TRAIL, both TRAIL-sensitive and partial resistant clones showed high levels of activation of caspase-3, caspase-8, RIP and PARP. |
| 970 | 12706864 | Relative basal level and induced level of Phosphoprotein over Expressed in Diabetes/Phosphoprotein Enriched in Astrocytes (PED/PEA-15) after TRAIL treatment were compared in the clones. |
| 971 | 12706864 | TRAIL did not change the PED/PEA-15 level in the clones. |
| 972 | 12706864 | In addition, transduction and expression of the dominant negative form of the I-kBalpha gene did not change TRAIL-sensitivities. |
| 973 | 12706864 | Our results showed that the expression levels of DR5, the activation levels of caspase-8, -3 and RIP were critical factors in determining TRAIL-sensitivities in Jurkat cells. |
| 974 | 12817789 | APS-1 is characterized by presence of chronic candidiasis, chronic hypoparathyroidism, Addison's disease. |
| 975 | 12817789 | It is a rare syndrome interesting particularly adult females and associated to a genetic pattern of HLA DR3/DR4. |
| 976 | 12843130 | Patients with PAS had significantly higher frequencies of the human leukocyte antigens A24, A31, B8, B51, B62, DR3, and DR4 (relative risk, 2.35, 2.74, 2.47, 7.17, 2.22, 1.94, and 2.46) vs. controls, and for A31, B15, B52, B55, DR2, DR11, and DR13 (relative risk, 2.51, 7.96, 3.99, 5.36, 4.46, 2.89, and 3.26) vs. type 1 diabetes patients without PAS. |
| 977 | 12859535 | In tacrolimus-converted children, age at transplant, mean and maximum tacrolimus blood levels, and first-year rejection episodes were higher in the post-transplant diabetes group, which also consistently had DR-mismatched transplants and HLA DR3/DR4 haplotypes. |
| 978 | 12941542 | In this study, we analyzed whether antibodies against CBV are increased in DR3, DR4, MICA5, or MICA5.1 positive patients from Linköping (n = 46) and from Swedish population as a whole (n = 298) between the age of 0 and 15 years old. |
| 979 | 14679079 | Frequency of diabetes risk-related alleles DQB1*0302, DQA1*0201, DR4, and DR3 was less prevalent among Lithuanian than among Swedish children with type 1 DM. |
| 980 | 15277401 | In this study, results are reported from testing these associations in three different sample sets: 1) Puerto Rican case and control subjects, 2) Mexican-American simplex families, and 3) high-risk (DR3/DR4) individuals with and without an affected relative. |
| 981 | 15620463 | One function of Lyp is downregulation of T-cell signaling through its interaction with the negative regulatory kinase C-terminal Src tyrosine kinase (Csk). |
| 982 | 15620463 | A single nucleotide polymorphism in the PTPN22 gene, C1858T, encodes products with different Csk binding affinities. |
| 983 | 15620463 | No effects of parent of origin, sex of patient, or human leukocyte antigen genotype (high-risk human leukocyte antigen DR3/DR4 vs non-DR3/DR4) were observed. |
| 984 | 15699512 | In addition, polymorphic MICA in HLA class I interacts with non-polymorphic NKG2D receptor on NK cells. |
| 985 | 15699512 | We have studied, in addition to HLA-DR and -DQ, genes of the innate immune system MICA and KIR in Latvian patients (n = 98) with T1DM and controls (n = 100). |
| 986 | 15699512 | KIR2DL2 and KIR2DS2 were both positively associated. |
| 987 | 15699512 | However, the combined risk of KIR2DL2 and HLA class II genes, HLADR3 (OR = 73.4), DR4 (OR = 66.8), and DR3 and DR4 (OR = 88.3), was higher. |
| 988 | 16249070 | Comparative study of GAD65-specific CD4+ T cells in healthy and type 1 diabetic subjects. |
| 989 | 16249070 | The prevalence of autoreactive CD4+ T cells towards the immunodominant GAD65(555-567) epitope in DR4 healthy and T1D subjects was investigated with class II tetramers. |
| 990 | 16249070 | A slightly higher percentage of diabetic subjects had GAD65(555-567) tetramer-positive T cells upon GAD65(555-567) peptide stimulation on the total CD4+ T-cell populations compared to healthy subjects. |
| 991 | 16249070 | In contrast, three quarters of subjects in both groups had tetramer-positive T cells resulting from stimulation of the CD4+CD25+ regulatory T-cell depleted CD4+ T cells. |
| 992 | 16249070 | These findings suggested that there is no difference in thymic selection of DR4 restricted GAD-reactive T cells amongst healthy and T1D individuals but GAD65(555-567)-reactive T cells have been preferentially activated in diabetic patients. |
| 993 | 16392185 | Despite histological arguments in favor of the mainly mechanical islet disturbances, an increased prevalence of anti-islets auto-antibodies and an increased frequency of HLA DR3/DR4 have been reported in cystic fibrosis population with glucose tolerance troubles. |
| 994 | 16483918 | The "Diabetogenic haplotypes" in Mexicans were DRB1*0301-DQA1*0501-DQB1*0201 (OR = 21.4); DRB1*0405-DQA1-*0301-DQB1*0302 (OR = 44.5) and the same DQA1/DQB1 with DRB1*0404/*0401 conferring lower risk, increasing (OR = 61.3) with an early age at onset and a heterozygote DR3/DR4 genotype. |
| 995 | 16554480 | Human astrocytes are resistant to Fas ligand and tumor necrosis factor-related apoptosis-inducing ligand-induced apoptosis. |
| 996 | 16554480 | Here, we report that calcium/calmodulin-dependent protein kinase II (CaMKII) is constitutively activated in human astrocytes and protects the cells from apoptotic stimulation by Fas agonist. |
| 997 | 16554480 | Once stimulated, Fas recruits Fas-associated death domain and caspase-8 for the assembly of the death-inducing signaling complex (DISC); however, caspase-8 cleavage is inhibited in the DISC. |
| 998 | 16554480 | Inhibition of CaMKII kinase activity inhibits the expression of phosphoprotein enriched astrocytes-15 kDa/phosphoprotein enriched in diabetes (PEA-15/PED) and cellular Fas-associated death domain-like interleukin-1beta-converting enzyme-inhibitory protein (c-FLIP), thus releasing their inhibition of caspase-8 cleavage. |
| 999 | 16554480 | Inhibition of PEA-15/PED or c-FLIP by small interfering RNA sensitizes human astrocytes to Fas-induced apoptosis. |
| 1000 | 16554480 | In contrast, inhibition of CaMKII, PEA-15, or c-FLIP does not affect the sensitivity of human astrocytes to tumor necrosis factor-related apoptosis-inducing ligand (TRAIL). |
| 1001 | 16554480 | TRAIL death receptors (DR4, DR5) are weakly expressed at mRNA, protein, and cell surface levels and thus fail to mediate the assembly of the DISC in human astrocytes. |
| 1002 | 16554480 | Overexpression of DR5 restores TRAIL signaling pathways and sensitizes the human astrocytes to TRAIL-induced apoptosis if CaMKII kinase activity or expression of PEA-15 and c-FLIP is inhibited; the results suggest that CaMKII-mediated pathways prevent TRAIL-induced apoptosis in human astrocytes under conditions in which TRAIL death receptors are upregulated. |
| 1003 | 16554480 | This study has therefore identified the molecular mechanisms that protect normal human astrocytes from apoptosis induced by Fas ligand and TRAIL. |
| 1004 | 16995591 | He had HLA A24, DR4 and DR53 antigens in common with previously reported cases of DM-NS association. |
| 1005 | 17435869 | We report two cases of dizygotic twins with type 1 diabetes onset in their first 9 months of age, with genetic homogeneity (for HLA DR3/DR4 alleles), a history of CMV infection (positive IgG and urinary PCR) and positive antibody anti-GAD (9.6 UI/ml), present only in the second twin. |
| 1006 | 17554341 | SUMO4 M55V polymorphism affects susceptibility to type I diabetes in HLA DR3- and DR4-positive Swedish patients. |
| 1007 | 17554341 | When we stratified our patients and controls based on heterozygosity for HLA-DR3/DR4 and SUMO4 genotypes, we found that presence of SUMO4 GG increased further the relative risk conferred by HLA-DR3/DR4 to TIDM, whereas SUMO4 AA decreased the risk. |
| 1008 | 17554341 | SUMO4 M55V polymorphism affects susceptibility to type I diabetes in HLA DR3- and DR4-positive Swedish patients. |
| 1009 | 17554341 | When we stratified our patients and controls based on heterozygosity for HLA-DR3/DR4 and SUMO4 genotypes, we found that presence of SUMO4 GG increased further the relative risk conferred by HLA-DR3/DR4 to TIDM, whereas SUMO4 AA decreased the risk. |
| 1010 | 17560173 | The HLA-DR3 and DR4 alleles are considered high risk factors for T1D and T(CD40) expansion occurs in T1D subjects carrying HLA DR3 or DR4 haplotypes but, T1D subjects who do not carry either DR3 or DR4 haplotypes still have an expanded percentage of T(CD40) cells. |
| 1011 | 17569614 | Resveratrol induces apoptosis by up-regulating the expression of Bax, Bak, PUMA, Noxa, Bim, p53, TRAIL, TRAIL-R1/DR4 and TRAIL-R2/DR5 and simultaneously down-regulating the expression of Bcl-2, Bcl-XL, Mcl-1 and survivin. |
| 1012 | 17569614 | Resveratrol causes growth arrest at G1 and G1/S phases of cell cycle by inducing the expression of CDK inhibitors p21/WAF1/CIP1 and p27/KIP1. |
| 1013 | 18486765 | Type 1 diabetes risk for human leukocyte antigen (HLA)-DR3 haplotypes depends on genotypic context: association of DPB1 and HLA class I loci among DR3- and DR4-matched Italian patients and controls. |
| 1014 | 18486765 | Patients (n = 133) with high-risk genotypes (DR3/DR3, DR3/DR4, DR4/DR4) were selected from the Lazio (Rome) region of Italy. |
| 1015 | 18486765 | Type 1 diabetes risk for human leukocyte antigen (HLA)-DR3 haplotypes depends on genotypic context: association of DPB1 and HLA class I loci among DR3- and DR4-matched Italian patients and controls. |
| 1016 | 18486765 | Patients (n = 133) with high-risk genotypes (DR3/DR3, DR3/DR4, DR4/DR4) were selected from the Lazio (Rome) region of Italy. |
| 1017 | 19432816 | DR5-mediated DISC controls caspase-8 cleavage and initiation of apoptosis in human glioblastomas. |
| 1018 | 19432816 | TRAIL has four membrane-anchored receptors, death receptor 4/5 (DR4/5) and decoy receptor 1/2 (DcR1/2). |
| 1019 | 19432816 | Of these receptors, only DR5 was expressed consistently in glioblastoma cell lines and tumour tissues, ruling out the role of DcR1/2 in TRAIL resistance. |
| 1020 | 19432816 | Upon TRAIL binding, DR5 was homotrimerized and recruited Fas-associated death domain (FADD) and caspase-8 for the assembly of death-inducing signalling complex (DISC) in the lipid rafts of the plasma membrane. |
| 1021 | 19432816 | In the DISC, caspase-8 was cleaved and initiated apoptosis by cleaving downstream caspases in TRAIL-sensitive glioblastoma cells. |
| 1022 | 19432816 | In TRAIL-resistant cells, however, DR5-mediated DISC was modified by receptor-interacting protein (RIP), cellular FADD-like interleukin-1beta-converting enzyme inhibitory protein (c-FLIP) and phosphoprotein enriched in diabetes or in astrocyte-15 (PED/PEA-15). |
| 1023 | 19432816 | This DISC modification occurred in the non-raft fractions of the plasma membrane and resulted in the inhibition of caspase-8 cleavage and activation of nuclear factor-kappaB (NF-kappaB). |
| 1024 | 19432816 | Treatment of resistant cells with parthenolide, an inhibitor of inhibitor of kappaB (I-kappaB), eliminated TRAIL-induced NF-kappaB activity but not TRAIL resistance. |
| 1025 | 19432816 | In contrast, however, targeting of RIP, c-FLIP or PED/PEA-15 with small interfering RNA (siRNA) led to the redistribution of the DISC from non-rafts to lipid rafts and eliminated the inhibition of caspase-8 cleavage and thereby TRAIL resistance. |
| 1026 | 19432816 | Taken together, this study indicates that the DISC modification by RIP, c-FLIP and PED/PEA-15 is the most upstream event in TRAIL resistance in glioblastomas. |
| 1027 | 19541464 | Autoantibody positivity is often accompanied by a high frequency of DR3 and DR4 alleles, which are classically related to the development of type 1 diabetes and, although not all studies agree on this point, by an immunological imbalance expressed by the behaviour of the lymphocyte subpopulation, which can be seen as diabetic anomalies overlapping with the immunological changes that occur during pregnancy. |
| 1028 | 19956102 | After stratification on the high T1D risk DR3/DR4 genotype, the variant (A) allele of C883A was significantly associated with T1D among non-DR3/DR4 cases (transmission=55.8%, P=0.004; OR=1.26) but was not significantly associated in the DR3/DR4 patient subgroup, replicating the earlier report. |
| 1029 | 19956102 | The reference A allele of intronic SNP rs17653687 was modestly associated with T1D in both DR3/DR4 strata (transmission=54.4% in DR3/DR4; P=0.03; transmission=52.9% in non-DR3/DR4; P=0.03). |
| 1030 | 19956102 | After stratification on the high T1D risk DR3/DR4 genotype, the variant (A) allele of C883A was significantly associated with T1D among non-DR3/DR4 cases (transmission=55.8%, P=0.004; OR=1.26) but was not significantly associated in the DR3/DR4 patient subgroup, replicating the earlier report. |
| 1031 | 19956102 | The reference A allele of intronic SNP rs17653687 was modestly associated with T1D in both DR3/DR4 strata (transmission=54.4% in DR3/DR4; P=0.03; transmission=52.9% in non-DR3/DR4; P=0.03). |
| 1032 | 20054343 | Using the transmission disequilibrium test, we compared the proportion of SNP alleles transmitted from within the high-risk DR3 and DR4 haplotypes to affected offspring. |
| 1033 | 20451496 | TRAIL upregulates decoy receptor 1 and mediates resistance to apoptosis in insulin-secreting INS-1 cells. |
| 1034 | 20451496 | TRAIL/Apo2L (tumor necrosis factor-related apoptosis-inducing ligand) is a multifunctional protein regulating the homeostasis of the immune system, infection, autoimmune diseases, and apoptosis. |
| 1035 | 20451496 | A previous study found that TRAIL did not have significant cytotoxic effects on the insulin-secreting pancreatic beta cell line, INS-1. |
| 1036 | 20451496 | TRAIL treatment showed NF-kappaB translocation to the nucleus in TRAIL-resistant INS-1 cells, and TRAIL-induced NF-kappaB activation was preceded by IkappaBalpha degradation. |
| 1037 | 20451496 | A pharmacological inhibitor of NF-kappaB, Bay 11-7082, blocked TRAIL-induced NF-kappaB translocation to the nucleus and IkappaBalpha degradation. |
| 1038 | 20451496 | Four related receptors bind TRAIL: two death receptors (DR4 and DR5) that promote apoptosis, and two decoy receptors (DcR1 and DcR2) that act as dominant-negative inhibitors of TRAIL-mediated apoptosis. |
| 1039 | 20451496 | In the present study, TRAIL treatment in INS-1 cells upregulated DcR1 and downregulated DR5 without altering the expression of DcR2 and DR4. |
| 1040 | 20451496 | The resistance to apoptosis in INS-1 cells might therefore, be a consequence of DcR1 upregulation and DR5 downregulation, and the transcription factor, NF-kappaB, could regulate the sensitivity of cells to TRAIL by controlling the ratio of decoy to death receptors. |
| 1041 | 20451496 | Thus, TRAIL may play an important role in the survival of pancreatic beta cells by regulating receptor expression in an NF-kappaB-dependent manner. |
| 1042 | 20451496 | TRAIL upregulates decoy receptor 1 and mediates resistance to apoptosis in insulin-secreting INS-1 cells. |
| 1043 | 20451496 | TRAIL/Apo2L (tumor necrosis factor-related apoptosis-inducing ligand) is a multifunctional protein regulating the homeostasis of the immune system, infection, autoimmune diseases, and apoptosis. |
| 1044 | 20451496 | A previous study found that TRAIL did not have significant cytotoxic effects on the insulin-secreting pancreatic beta cell line, INS-1. |
| 1045 | 20451496 | TRAIL treatment showed NF-kappaB translocation to the nucleus in TRAIL-resistant INS-1 cells, and TRAIL-induced NF-kappaB activation was preceded by IkappaBalpha degradation. |
| 1046 | 20451496 | A pharmacological inhibitor of NF-kappaB, Bay 11-7082, blocked TRAIL-induced NF-kappaB translocation to the nucleus and IkappaBalpha degradation. |
| 1047 | 20451496 | Four related receptors bind TRAIL: two death receptors (DR4 and DR5) that promote apoptosis, and two decoy receptors (DcR1 and DcR2) that act as dominant-negative inhibitors of TRAIL-mediated apoptosis. |
| 1048 | 20451496 | In the present study, TRAIL treatment in INS-1 cells upregulated DcR1 and downregulated DR5 without altering the expression of DcR2 and DR4. |
| 1049 | 20451496 | The resistance to apoptosis in INS-1 cells might therefore, be a consequence of DcR1 upregulation and DR5 downregulation, and the transcription factor, NF-kappaB, could regulate the sensitivity of cells to TRAIL by controlling the ratio of decoy to death receptors. |
| 1050 | 20451496 | Thus, TRAIL may play an important role in the survival of pancreatic beta cells by regulating receptor expression in an NF-kappaB-dependent manner. |
| 1051 | 20580654 | The genotype 2DL1/C2+ was also more common in controls (p = 0.001), as well as haplotype association KIR2DL2/DR3/DR4+ and the combination with only DR3+ (p < 0.001; p < 0.001). |
| 1052 | 20580654 | The maximum protection was seen when KIR2DL2/DR3-were absent when the combination of KIR2DL1/C2+ were present (p < 0.001) and the maximum risk was observed when KIR2DL2/DR3/DR4+ were present in the absence of KIR2DL1/C2- (p = 0.005). |
| 1053 | 20580654 | Our results confirmed the association of the KIR2DL2/DR3 increasing risk for T1D and suggest a protective role of KIR2DL1/C2. |
| 1054 | 20580654 | The genotype 2DL1/C2+ was also more common in controls (p = 0.001), as well as haplotype association KIR2DL2/DR3/DR4+ and the combination with only DR3+ (p < 0.001; p < 0.001). |
| 1055 | 20580654 | The maximum protection was seen when KIR2DL2/DR3-were absent when the combination of KIR2DL1/C2+ were present (p < 0.001) and the maximum risk was observed when KIR2DL2/DR3/DR4+ were present in the absence of KIR2DL1/C2- (p = 0.005). |
| 1056 | 20580654 | Our results confirmed the association of the KIR2DL2/DR3 increasing risk for T1D and suggest a protective role of KIR2DL1/C2. |
| 1057 | 22385239 | In this study we showed that peripheral sera cytokines [interleukin (IL)-12, IL-6, II-1β, tumour necrosis factor (TNF)-α, IL-10] and chemokines (CXCL10, CXCL8, CXCL9, CCL2) measured were significantly higher in newly diagnosed T1AD patients when compared to healthy controls (P < 0·001). |
| 1058 | 22385239 | Among T1AD, we found a positive correlation between CXCL10 and CCL-2 (r = 0·80; P = 0·000), IL-8 and TNF-α (r = 0·60; P = 0·000); IL-8 and IL-12 (r = 0·57; P = 0·001) and TNF-α and IL-12 (r = 0·93; P = 0·000). |
| 1059 | 22385239 | Glutamic acid decarboxylase-65 (GAD-65) autoantibodies (GADA) were associated negatively with CXCL10 (r = -0·45; P = 0·011) and CCL2 (r = -0·65; P = 0·000), while IA-2A showed a negative correlation with IL-10 (r = -0·38; P = 0·027). |
| 1060 | 22385239 | Human leucocyte antigen (HLA) DR3, DR4 or DR3/DR4 and PTPN22 polymorphism did not show any association with pancreatic islet cell antibodies or cytokines studied. |
| 1061 | 23480181 | The PTPN22 1858T allele but not variants in the proximal promoter region of IL-21 gene is associated with the susceptibility to type 1 diabetes and the presence of autoantibodies in a Brazilian cohort. |
| 1062 | 23480181 | Interleukin (IL)-21 and protein tyrosine phosphatase non-receptor 22 (PTPN22) regulate lymphocyte function and have been implicated in the pathogenesis of autoimmune diabetes. |
| 1063 | 23480181 | We sequenced the proximal promoter of the IL-21 gene for the first time and analysed the PTPN22 1858T polymorphism in type 1A diabetes (T1AD) patients and healthy controls (HC). |
| 1064 | 23480181 | We also evaluated human leucocyte antigen (HLA) DR3/DR4 alleles. |
| 1065 | 23480181 | The frequencies of glutamic acid decarboxylase (GAD65), tyrosine phosphatase-like protein (IA)-2, anti-nuclear antibody (ANA), thyroid peroxidase (TPO), thyroglobulin (TG), thyrotrophin receptor autoantibody (TRAb), anti-smooth muscle (ASM) and 21-hydroxylase (21-OH) autoantibodies were higher in T1AD patients than in HC. |
| 1066 | 23480181 | The PTPN22 1858T allele was associated with an increased risk for developing T1AD [odds ratio (OR) = 1·94; P < 0·001], particularly in patients of European ancestry, and with a higher frequency of GAD65 and TG autoantibodies. |
| 1067 | 23480181 | In conclusion, only PTPN22 C1858T polymorphism and HLA-DR3 and/or DR4 alleles, but not allelic variants in the 5'-proximal region of the IL-21 gene were associated with T1AD risk. |
| 1068 | 23480181 | The C1858T PTPN22 polymorphism was also associated with a higher frequency of GAD65 and TG autoantibodies. |