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. 2010 Nov;59(11):2972-9.
doi: 10.2337/db10-0699. Epub 2010 Aug 26.

HLA class I and genetic susceptibility to type 1 diabetes: results from the Type 1 Diabetes Genetics Consortium

Janelle A Noble  1 , Ana Maria Valdes, Michael D Varney, Joyce A Carlson, Priscilla Moonsamy, Anna Lisa Fear, Julie A Lane, Eva Lavant, Rebecca Rappner, Anthony Louey, Patrick Concannon, Josyf C Mychaleckyj, Henry A Erlich; Type 1 Diabetes Genetics Consortium
Affiliations

HLA class I and genetic susceptibility to type 1 diabetes: results from the Type 1 Diabetes Genetics Consortium

Janelle A Noble et al. Diabetes. 2010 Nov.

Abstract

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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Figures

FIG. 1.
FIG. 1.
LD diagram for selected HLA alleles. The r2 × 100 value of LD between pairs of alleles is shown.
See this image and copyright information in PMC

References

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