The HLA class I A locus affects susceptibility to type 1 diabetes

Abstract

Human leukocyte antigen A (HLA-A) genotypes were determined for samples from 283 multiplex, Caucasian, type 1 diabetes families from the Human Biological Data Interchange (HBDI) using an immobilized probe assay. Distribution of HLA-A alleles transmitted to patients was significantly different from that in affected family-based controls (AFBAC) (p = 0.004). Transmission disequilibrium test (TDT) analysis revealed differential transmission of several HLA-A alleles from parents to affected offspring. HLA class II DRB1 and DQB1 loci were also typed, allowing assignment of HLA-A alleles to haplotypes and calculation of linkage disequilibrium values. Some of the apparent effects of HLA-A alleles on type 1 diabetes susceptibility were attributable to linkage disequilibrium with DR and DQ alleles, although others were not. The differences in frequencies between patients and controls of alleles A*0101, A*2402, and A*3002 could not be explained by linkage disequilibrium alone. Our results suggest an important role for class I antigens in modulating susceptibility to type 1 diabetes.

FIGURE 1

Odds ratio, calculated based on observed versus expected frequencies given linkage disequilibrium with DR-DQ, and 95% confidence intervals for alleles A*0101 and A*2401 in three different age of onset categories (age of onset > 0 and ≤ 5 years old, age of onset > 5 and ≤ 12 years old, and age of onset > 12 years old).