ACE基因、AT1R基因多态性与2型糖尿病肾病的关系

Association between gene polymorphisms of ACE and AT1R and diabetic nephropathy in Chinese type 2 diabetes

目的研究血管紧张素I转化酶(ACE)基因/D多态及血管紧张素受体1型(AT1R)A1166C多态性与中国汉族人2型糖尿病肾病(DN)的关系。方法运用聚合酶链反应(PCR)和PCR/DdeI酶切技术,检测93例DN患者(DN组)与94例2型糖尿病患者(DM组)ACE基因及AT1R基因多态基因型。结果DN组ACE基因DD基因型频率(34.4%)、D型等位基因频率(54.3%)较DM组(19.1%,40.4%)均升高(P<0.05,<0.01);两组间AT1R基因A1166C多态基因型频率和等位基因频率分布均无差异(P>0.05);ACE和AT1R基因多态与DN的分层分析显示,同时携带ACE纯合子缺失基因型(DD)和AT1R突变基因型(AC+CC)者发生DN的危险较大,OR值为8.569。结论ACE基因/D多态性与2型DM并发DN有关,携带DD基因型和D型等位基因的2型DM患者是DN的易感人群。ATlR基因A1166C多态性虽与我国汉族人2型DM并发DN无关,但AT1R与ACE基因多态存在协同效应,携带AC+CC与DD基因型的个体有更高的患DN风险。

Objective To study the association between gene polymorphisms of angiotensin Ⅰ coverting enzyme(ACE) and type 1 angiotensin Ⅱ receptor(AT1R) and diabetic nephropathy(DN) in Chinese type 2 diabetes.Methods PCR and PCR/DdeⅠ techniques were used to identify the ACE and AT1R gene polymorphisms in Chinese type 2 diabetes with nephropathy (DN group,n=93) and without nephropathy(DM group,n=94).Results The ACE DD genotype and D allele frequencies were significantly higher in DN group than in DM group(34.4% vs 19.1%,P<0.05; 54.3% vs 40.4%,P<0.01,respectively).No statistically significant differences between groups were found in the allele frequency and genotype distribution for AT1R polymorphism.Stratified analysis between ACE and AT1R gene polymorphisms was shown that individuals carrying both ACE-DD homozygotes and AT1R-AC+CC genotypes increased susceptibility to DN(OR=8.569,95%CI:1.025~71.665).Conclusion ACE gene I/D polymorphism is associated with DN in Chinese type 2 diabetes while AT1R A1166C polymorphism is not.DD genotype and D allele of ACE gene may correlate with a predisposing factor for DN.There is synergistic effect of AT1R A1166C and ACE Ⅰ/D gene polymorphisms on the occurrence of DN,and type 2 diabetic patients with both DD and AC+CC genotypes have much higher risk of occurring DN.