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. 2011 Jul;54(7):1702-9.
doi: 10.1007/s00125-011-2161-1. Epub 2011 May 1.

The HLA-B 3906 allele imparts a high risk of diabetes only on specific HLA-DR/DQ haplotypes

E E Baschal  1 , P R Baker, K R Eyring, J C Siebert, J M Jasinski, G S Eisenbarth
Affiliations

The HLA-B 3906 allele imparts a high risk of diabetes only on specific HLA-DR/DQ haplotypes

E E Baschal et al. Diabetologia. 2011 Jul.

Abstract

Aims/hypothesis: We investigated the risk associated with HLA-B*39 alleles in the context of specific HLA-DR/DQ haplotypes.

Methods: We studied a readily available dataset from the Type 1 Diabetes Genetics Consortium that consists of 2,300 affected sibling pair families genotyped for both HLA alleles and 2,837 single nucleotide polymorphisms across the major histocompatibility complex region.

Results: The B*3906 allele significantly enhanced the risk of type 1 diabetes when present on specific HLA-DR/DQ haplotypes (DRB1 0801-DQB1 0402: p = 1.6 × 10(-6), OR 25.4; DRB1 0101-DQB1 0501: p = 4.9 × 10(-5), OR 10.3) but did not enhance the risk of DRB1 0401-DQB1 0302 haplotypes. In addition, the B 3901 allele enhanced risk on the DRB1 1601-DQB1 0502 haplotype (p = 3.7 × 10(-3), OR 7.2).

Conclusions/interpretation: These associations indicate that the B 39 alleles significantly increase risk when present on specific HLA-DR/DQ haplotypes, and HLA-B typing in concert with specific HLA-DR/DQ genotypes should facilitate genetic prediction of type 1 diabetes, particularly in a research setting.

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Figures

Fig. 1
Fig. 1
Comparison of HLA-B alleles based on SNPs. Each column is a chromosome and each row is a SNP. aHLA-B*3906 chromosomes compared with HLA-B*3906 consensus (124 chromosomes, 219 SNPs and 0.26 Mb). bHLA-B*3901 chromosomes compared with HLA-B*3906 consensus (80 chromosomes, 219 SNPs and 0.26 Mb). cHLA-B*1402 chromosomes compared with HLA-B*3906 consensus (144 chromosomes, 219 SNPs and 0.26 Mb). The same consensus sequence was used in a–c, and was based on B*3906 chromosomes. The chromosomes are organised by HLA-DR/DQ type in each figure part, and only the region surrounding the HLA-B gene is shown. Yellow boxes show that the allele matches that of the B*3906 consensus, whereas blue represents the opposite allele. The telomeric end of the MHC is at the top of the graph. Type 1 diabetes case chromosomes are on the left and control chromosomes are on the right
See this image and copyright information in PMC

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