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目的研究湖北地区2型糖尿病(type2diabetes mellitus,T2DM)中线粒体基因突变的发生率及其相关性。方法采用聚合酶链反应-限制性片段长度多态性及DNA测序技术,对184例2型糖尿病患者和210名糖耐量正常的健康对照进行检测,并用mfold和tRNAscan-SE软件对检出的突变位点进行二级结构分析。结果MIND13316(G→A)、MIND13394(T→C)、D环区16189(T→C)变异率分别为3.26%、2.72%、36·9%,并首次在T2DM中发现4例MTTE14693(A→G)突变(2.17%);对照组检出3316(G→A)突变2例(0·99%)、16189(T→C)变异56例(26.6%),未检出3394、14693的点突变;两组间3394(T→C)、14693(A→G)、16189(T→C)变异率差别均有统计学意义(P<0.05);且T2DM组中16189(T→C)变异阳性者的胰岛素抵抗指数(HOMA-IR)值较16189(T→C)变异阴性组升高,差异有统计学意义(P=0.028);多元回归分析显示该变异为参与HOMA-IR的独立变量(R2=0.043,P=0.037)。RNA二级结构预测发现,3394(T→C)和14693(A→G)突变使其相应的二级结构发生变化。结论3394(T→C)、14693(A→G)突变与T2DM的易感性有一定关联,16189(T→C)变异与湖北地区汉族人T2DM胰岛素抵抗相关。
Objective To investigate the incidence of mitochondrial DNA mutations in type 2 diabetes mellitus (T2DM) in Hubei Province and their correlation. Methods A total of 184 patients with type 2 diabetes and 210 healthy controls with normal glucose tolerance were detected by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) and DNA sequencing. The mutations were detected by mfold and tRNAscan-SE software Secondary structure analysis. Results The mutation rates of 16189 (T → C) in MIND13316 (G → A), MIND13394 (T → C) and D loop were 3.26%, 2.72% and 36.9%, respectively. (2.17%) in the control group. There were 2 cases (33.9%) in the control group, 56 cases (26.6%) in 16189 (T → C) mutation, 3394 (T → C), 14693 (A → G) and 16189 (T → C) in the two groups were significantly different between the two groups (P> 0.05) The HOMA-IR of patients with positive mutation was significantly higher than that of negative patients with 16189 (T → C) mutation (P = 0.028). Multiple regression analysis showed that HOMA-IR was independent of HOMA-IR Variable (R2 = 0.043, P = 0.037). RNA secondary structure prediction found 3394 (T → C) and 14693 (A → G) mutations to the corresponding secondary structure changes. Conclusion The mutations of 3394 (T → C) and 14693 (A → G) are correlated with the susceptibility to T2DM. The mutation of 16189 (T → C) is associated with insulin resistance in T2DM Han population in Hubei Province.