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HLA Class I and Genetic Susceptibility to Type 1 Diabetes: Results From the Type 1 Diabetes Genetics Consortium
OBJECTIVE: We report here genotyping data and type 1 diabetes association analyses for HLA class I loci (A, B, and C) on 1,753 multiplex pedigrees from the Type 1 Diabetes Genetics Consortium (T1DGC), a large international collaborative study. RESEARCH DESIGN AND METHODS: Complete eight-locus HLA ge...
Autores principales: | , , , , , , , , , , , , |
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Formato: | Texto |
Lenguaje: | English |
Publicado: |
American Diabetes Association
2010
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2963558/ https://www.ncbi.nlm.nih.gov/pubmed/20798335 http://dx.doi.org/10.2337/db10-0699 |
Sumario: | OBJECTIVE: We report here genotyping data and type 1 diabetes association analyses for HLA class I loci (A, B, and C) on 1,753 multiplex pedigrees from the Type 1 Diabetes Genetics Consortium (T1DGC), a large international collaborative study. RESEARCH DESIGN AND METHODS: Complete eight-locus HLA genotyping data were generated. Expected patient class I (HLA-A, -B, and -C) allele frequencies were calculated, based on linkage disequilibrium (LD) patterns with observed HLA class II DRB1-DQA1-DQB1 haplotype frequencies. Expected frequencies were compared to observed allele frequencies in patients. RESULTS: Significant type 1 diabetes associations were observed at all class I HLA loci. After accounting for LD with HLA class II, the most significantly type 1 diabetes–associated alleles were B*5701 (odds ratio 0.19; P = 4 × 10(−11)) and B*3906 (10.31; P = 4 × 10(−10)). Other significantly type 1 diabetes–associated alleles included A*2402, A*0201, B*1801, and C*0501 (predisposing) and A*1101, A*3201, A*6601, B*0702, B*4403, B*3502, C*1601, and C*0401 (protective). Some alleles, notably B*3906, appear to modulate the risk of all DRB1-DQA1-DQB1 haplotypes on which they reside, suggesting a class I effect that is independent of class II. Other class I type 1 diabetes associations appear to be specific to individual class II haplotypes. Some apparent associations (e.g., C*1601) could be attributed to strong LD to another class I susceptibility locus (B*4403). CONCLUSIONS: These data indicate that HLA class I alleles, in addition to and independently from HLA class II alleles, are associated with type 1 diabetes. |
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