Polymorphisms of HLA-DQA1 and the DQA1 promoter region in insulin-dependent diabetes mellitus

Objective To investigate the association between polymorphism ofHLA-DQA1, DQA1 promoter region (QAP) and susceptibility of insulin-dependent diabetes mellitus (IDDM). Methods PCR-RFLP and PCR-SSO gene typing techniques were used to detect HLA-DQA1 alleles and their promoter regions respectively. Results Alleles analysis showed that frequencies of DQA1*0301 and QAP3.2 were significantly increased in the diabetic patients compared to controls (RR=2.80, 2.43, P<0.01), whereas frequencies of DQA1*0601,QAP4.2 were significantly decreased in patients (RR=0.10, P<0.025). The analysis of combinations between promoter and coding gene showed that QAP3.2-DQA1*0301 but not QAP3.1-DQA1*0301 contributes to disease susceptibility, and QAP4.2-DQA1*0601 contributes to protection. Conclusions 1. Susceptibility of IDDM is not restricted to the exon but extends to the promoter region. 2. The same exon linked with different promoters showed different genetic risk for IDDM.