Genomic evaluation of HLA-DR3+ haplotypes associated with type 1 diabetes.

Neeraj Kumar, Gurvinder Kaur, Nikhil Tandon, Uma Kanga, Narinder K Mehra

Department of Transplant Immunology and Immunogenetics, All India Institute of Medical Sciences, Ansari Nagar, New Delhi, India.

Annals of the New York Academy of Sciences 2013 Apr

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We have defined three sets of HLA-DR3(+) haplotypes that provide maximum risk of type 1 disease development in Indians: (1) a diverse array of B8-DR3 haplotypes, (2) A33-B58-DR3 haplotype, and (3) A2-B50-DR3 occurring most predominantly in this population. Further analysis has revealed extensive diversity in B8-DR3 haplotypes, particularly at the HLA-A locus, in contrast to the single fixed HLA-A1-B8-DR3 haplotype (generally referred to as AH8.1) reported in Caucasians. However, the classical AH8.1 haplotype was rare and differed from the Caucasian counterpart at multiple loci. In our study, HLA-A26-B8-DR3 (AH8.2) was the most common B8-DR3 haplotype constituting >50% of the total B8-DR3 haplotypes. Further, A2-B8-DR3 contributed the maximum risk (RR = 48.7) of type 1 diabetes, followed by A2-B50-DR3 (RR = 9.4), A33-B58-DR3 (RR = 6.6), A24-B8-DR3 (RR = 4.5), and A26-B8-DR3 (RR = 4.2). Despite several differences, the disease-associated haplotypes in Indian and Caucasian populations share a frozen DR3-DQ2 block, suggesting a common ancestor from which multiple haplotypes evolved independently. © 2013 The New York Academy of Sciences.

Citation

Neeraj Kumar, Gurvinder Kaur, Nikhil Tandon, Uma Kanga, Narinder K Mehra. Genomic evaluation of HLA-DR3+ haplotypes associated with type 1 diabetes. Annals of the New York Academy of Sciences. 2013 Apr;1283:91-6