HLA class II polymorphism in Thai insulin-dependent diabetes mellitus.

Abstract

Fifty-seven Thai IDDM patients were studied for HLA class I by LCT and HLA class II by LCT and PCR-RFLP. It was found that DRB1*0301, DR3, DQB1*0201, DRB3*0202, DQA1*0501 and DQ2 were significantly increased with R.R. = 10.0, 6.6, 4.2, 3.7, 3.5 and 3.2 and Pc < 0.005, 0.001, 0.01, 0.005, 0.01 and 0.005, respectively. In contrast, DQA1*0101, DRB3*0301, DR5 and DQ1 were significantly decreased with R.R. = 0.2, 0.2, 0.3 and 0.5 and Pc < 0.01, 0.05, 0.01 and 0.05, respectively. The primary factor for IDDM susceptibility is probably DRB1. The homozygous Asp57/Asp57 DQB1 genotype appears to determine resistance to IDDM while Arg52-DQA1, non-Asp57-DQB1 haplotype confers susceptibility to IDDM. The common haplotypes in Thai IDDM cases were DRB1*0301, DRB3*0202, DQA1*0501, DQB1*0201, DPB1*0401 and DRB1*0405, DQA1*0301, DQB1*0402 (or 0401 or 0302), DPB1*0401 (or 0301 or 1501). The less common haplotypes were DRB1*0406, DQA1*0301, DPB1*0302, DPB1*0501 and DRB1*1202, DRB1*0301, DQA1*0601, DQB1*0301, DPB1*0501. DR3 was increased in both gender groups with early onset (< 10 years) regardless of a family history of DM. However, DR3/DR4 genotype was increased only in female patients with a family history of DM and early onset. In conclusion, DRB1, DRB3, DQA1 and DQB1, but not DPB1 are involved in the occurrence of IDDM. The cooperation of HLA class II and X-chromosome may contribute to the development of IDDM in addition to other factors such as other genetic (chromosomes 11, 19, 14, 7), immunologic and environmental factors which require further study.