基质金属蛋白酶9基因多态性与2型糖尿病血管病变的相关性研究

目的 探讨基质金属蛋白酶9(MMP-9)基因C-1562T多态性与2型糖尿痫血管病变的关系．方法 运用PCR-RFLP检测110名健康对照者和450例2型糖尿病(DM)患者(其中单纯2型DM者100例、大血管病变者120例、糖尿病肾病(DN)患者130例、糖尿病视网膜病变患者100例)的MMP-9基因型，比较各组的基因型和等位基因频率。结果 (1)所有糖尿病视网膜病变患者的基因型均为CC型。(2)与对照组和单纯2型DM组相比，大血管病变组的T基因型和T等位基因频率显著升高，而DN组的TT基因型和T等位基因频率明显下降。(3)Logistic回归分析显示MMP-9 T等位基因、血清MMP-9、总胆固醇、低密度脂蛋白胆固醇、脂蛋白(a)是大血管病变发生的危险因素；尿白蛋白排泄率、脂蛋白(a)、HbA1C是DN发生的危险因素。结论 MMP-9基因C-1562T多态性与2型DM血管病变的发生有关，T等位基因是大血管病变的易感基因，是DN的保护基因。

Association of matrix metalloproteinase-9 gene polymorphism to angiopathy in type 2 diabetes mellitus

Objective To investigate the association of matrix metalloproteinase-9 (MMP-9) C-1562T gene polymorphism to angiopathy in type 2 diabetes mellitus. Methods MMP-9 genotype was determined by PCR-RFLP in 110 healthy controls and 450 patients with type 2 diabetes including 100 complication-free cases, 120 with macroangiopathy, 130 with diabetic nephropathy (DN) and 100 with diabetic retinopathy (DR). MMP-9 genotype and allele frequencies were compared among groups. Results (1) All DR patients were CC genotype. (2) Compared with healthy controls and diabetic patients without complication, patients with macroangiopathy had higher frequencies of TT genotype and T allele, while the frequencies of TT genotype and T allele were lower in diabetic nephropathy group. (3) Multivariate logistic regression analysis showed that MMP-9 T allele, serum MMP-9, total cholesterol, low density lipoprotein-cholesterol, lipoprotein (a) were the important risk factors of diabetic macroangiopathy, while urinary albumin excretion rate, lipoprotein (a) and HbA_ 1C were the risk factors of DN. Conclusion MMP-9 C-1562T gene polymorphism is associated with the development of angiopathy in type 2 diabetes mellitus. T allele is a susceptible gene of diabetic macroangiopathy and a protective gene of DN.