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The major histocompatibility complex (MHC) HLA region on chromosome 6p21 contains the major locus of type 1 diabetes (IDDM1). Common allelic variants at the class II HLA-DRB1, -DQA1, and -DQB1 loci account for the major part of IDDM1. Previous studies suggested that other MHC loci are likely to contribute to IDDM1, but determination of their relative contributions and identities is difficult because of strong linkage disequilibrium between MHC loci. One prime candidate is the polymorphic HLA-DPB1 locus, which (with the DPA1 locus) encodes the third class II antigen-presenting molecule. However, the results obtained in previous studies appear to be contradictory. Therefore, we have analyzed 408 white European families (200 from Sardinia and 208 from the U.K.) using a combination of association tests designed to directly compare the effect of DPB1 variation on the relative predisposition of DR-DQ haplotypes, taking into account linkage disequilibrium between DPB1 and the DRB1, DQA1, and DQB1 loci. In these populations, the overall contribution of DPB1 to IDDM1 is small. The main component of the DPB1 contribution to IDDM1 in these populations appears to be the protection associated with DPB1*0402 on DR4-negative haplotypes. We suggest that the HLA-DP molecule itself contributes to IDDM1.

Original publication

DOI

10.2337/diabetes.50.5.1200

Type

Journal article

Journal

Diabetes

Publication Date

05/2001

Volume

50

Pages

1200 - 1205

Keywords

Alleles, Chromosome Mapping, Chromosomes, Human, Pair 6, Confidence Intervals, Diabetes Mellitus, Type 1, Genetic Predisposition to Disease, Genetic Variation, HLA-DP Antigens, HLA-DP beta-Chains, HLA-DQ Antigens, HLA-DQ alpha-Chains, HLA-DQ beta-Chains, HLA-DR Antigens, HLA-DRB1 Chains, Haplotypes, Humans, Italy, United Kingdom