Asian-Specific HLA Haplotypes Reveal Heterogeneity of the Contribution of HLA-DR and -DQ Haplotypes to Susceptibility to Type 1 Diabetes

Abstract

To assess the effect of Asian-specific HLA liaplotypes on susceptibility to type 1 diabetes, we investigated the association of genotypic combinations of DRB1-DQB1 haplotypes with susceptibility to type 1 diabetes. We studied 132 Japanese patients with type 1 diabetes and 157 control subjects, along with 67 Korean patients and 109 control subjects. DRB1WM05-DQB1 *0401 and DRB1 *0901-DQB1 *0S03 were confirmed to be two major susceptible HLA haplotypes in the Japanese pop¬ulation. The frequencies of heterozygotes and honiozy- gotes with DRB1WW5-DQB1W401 were similarly higher in patients than in control subjects (liomozy- gotes, 5.3% vs. 3.8%; heterozygotes, 48.5% vs. 26.1%). In contrast, homozygotes, but not heterozygotes, with DRB1 *0901-DQB1 *0303 were more frequent in patients with type 1 diabetes than in control subjects (homozy¬gotes, 12.9% vs. 0.6%; heterozygotes, 22.0% vs. 24.8%). A similar tendency was also observed in the Korean population. In multiple logistic regression analysis, DRB1*0¥)5-DQB1W사01 fitted a dominant model and DRB1 "0901-DQB1W303 fitted a recessive model. These data, which indicate that the contribution of HLA hap¬lotypes to the genetic susceptibility to type 1 diabetes differs depending on the genotypic combination of HLA haplotypes, suggest the Importance of extensive analy¬sis of genotypes in studies on HLA and disease associa¬tion in general. Diabetes 51:545-551, 2002