HLA-DMA and HLA-DMB alleles in German patients with type 1 diabetes mellitus.

Abstract

The HLA-DMA and HLA-DMB genes are located in the HLA-D region between DQ and DP. Four variants of DMA (DMA*0101-0104) and five of the DMB (DMB*0101-0105) have so far been identified. HLA-DM molecules are required in the process of peptide loading to HLA class II antigens, both regulating the dissociation of class II-associated invariant chain peptides (CLIP) and the subsequent binding of exogenous peptides to HLA class II molecules. In order to investigate the immunogenetic heterogeneity within the HLA-D susceptibility region, we analysed the distribution of DMA alleles in 125 patients with type 1 diabetes mellitus and 90 healthy controls, and of DMB alleles in 102 patients and 89 healthy controls. Patients and controls were all from central Germany. The polymerase chain reaction (PCR) amplified products were purified and separated on a 10% polyacrylamide gel electrophoresis. Among the four recognized DMA alleles, DMA*0102 was significantly less frequent (12% vs. 28.9%, P<0.01) in patients with type 1 diabetes mellitus. DMB*0101 (70.6% vs. 97.8%, P<5.5x10(-3)) was also reduced in frequency compared to controls. Comparing patients and controls positive for the type 1 diabetes high-risk markers we found a significant association between DMA*0102 and DQA*0501 (9.5% vs. 39.1%, P<0.02), as well as DMB*0101 and DQA*0501 (62.5% vs. 96.2%, P<0.03). In conclusion, DMA*0102 and DMB*0101 contribute to genetic protection to type 1 diabetes mellitus in individuals with high-risk DQA markers in the German population.