HLA class II alpha chain gene polymorphisms in patients with insulin-dependent diabetes mellitus, dermatitis herpetiformis, and celiac disease

Abstract

We have investigated DNA polymorphism of the class IIα chain genes in HLA types patients with insulin dependent diabetes mellitus (IDDM; n = 79), celiac disease (CD; n = 46), dermatitis herpetiformic (DH; n = 53), and controls (n = 86). Preferential allelic associations of HLA genes and gene products have thus been constructed for susceptibility to these diseases. DRα and DQα gene polymorphisms indicated heterogeneity of HLA DR3, DRw6, and DR7, and HLA DR2 and DRw6, respectively. In DR7 positive CD patients a 3.8-kilobase (kb) DRα fragment, which correlated with DQw3, was found in only 11% of patients compared with 45% of corresponding controls (P < 0.05). An increased frequency of a DXα genotype UU in all three diseases was found (IDDM 59%, DH 45%, CD 48%, compared to 21% in controls, P < 0.001), which is not explained solely by the increased frequencies of DR3-DXαU. We therefore conclude part of the genetic susceptibility for these three conditions is encoded by genes within the DQ-DX subregion.