线粒体基因ND1/T3394C突变与糖尿病

Mitochondrial ND1/T3394C Mutations Associated with Diabetes Mellitus in Chinese

【目的】调查线粒体NADH脱氢酶亚单位 1(ND1)基因的T3394C位点突变与中国人糖尿病的发病情况。【方法】随机收集 338例无血缘关系的糖尿病患者及 2 6 2例正常对照组 ,用聚合酶链反应扩增、限制性内切酶HaeⅢ消化进行突变筛查 ,DNA序列分析确认。【结果】糖尿病患者中T3394C突变者共 8例 (2 37%) ,正常对照组中只有 1例 (0 38%,P <0 0 1)。糖尿病突变患者中 4例有糖尿病家族史 ,4例病人由于胰岛素分泌功能下降和 /或出现并发症 ,需用胰岛素治疗。【结论】ND1/T3394C突变在糖尿病患者中的发生率明显高于正常对组 ,提示这个位点突变可能是导致线粒体糖尿病的易感基因之一。

Objective To investigate the contribution of the ND1/3394 mutations in mitochondrial genes to the development of diabetes in Chinese diabetic population. MethodsUsing PCR-HaeⅢ-RFLP and PCR product direct sequencing techniques, 338 randomly selected Chinese patients with diabetes mellitus without prior information about type of diabetes, age of onset, family history, mode of therapy, or any other clinical features, and 262 nondiabetic control subjects were examined. ResultsA homoplasmic mutation at position 3394 T-C was observed in 2.37% of diabetic patients and 0.38% of nondiabetic controls. The frequency was significantly higher in the diabetic patients than in the control subjects. Among eight unrelated subjects with 3394 mutation, half of them required insulin therapy due to secondary failure to oral hypoglycemic agents and / or decreased insulin secretory capacity.Conclusion The high incidence of mutations in Chinese diabetic patients suggests that the ND1/3394 is associated with diabetes mellitus. Clinical features of the patients with the ND1/3394 mutation are similar to that of type 2 diabetes mellitus.