IDDM与HLA-DQA1及其启动子QAP 的相关性研究

目的 研究胰岛素依赖性糖尿病（IDDM）的易感性与HLA－DQA1及其启动子QAP基因多态性是否存在关联。方法 采用PCR－RFLP分析DQA1等位基因多态性；采用PCR－SSO检测QAP多态性。结果 等位基因分析发现，患者中DQA1＊0301、QAP3．2等位基因频率显著高于正常人（RR＝2．80、2．43，P＜0．01）；而DQA1＊0601、QAP4．2在患者中分布频率较正常人显著降低（RR＝0．10，P＜0．025）。启动子与结构基因连锁分析表明：QAP3．2－DQA1＊0301单元型与IDDM关联，QAP3．1－DQA1＊0301与IDDM无关联；QAP4．20－DQA1＊0601则具有保护作用。结论 1．IDDM与HLA的关联不仅存在于结构基因，而且也存在于启动子；2．同一结构基因与不同的启动子连锁可呈现不同的关联格局。

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

Objective To investigate the association between polymorphism of HLA 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.