2型糖尿病人群线粒体基因16189T/C的变异

Variation of mitochondrial DNA 16189T/C in type 2 diabetics

目的:研究线粒体基因16189T/C变异在2型糖尿病人群中的发生率和该基因变异与胰岛素抵抗和胰岛素分泌功能的关系。方法:采聚和酶链反应和限制性片段长度多态性分析技术对155例吉林大学第二医院住院的2型糖尿病患者(病例组)和164例同期住院患者及部分病例组人员爱人(正常对照组)的线粒体基因16189T/C突变情况进行筛检,并比较两组的一般状况和部分代谢指标。结果:①得到3种酶切图谱:229bp纯合未切开,代表基因序列中无限制酶切位点,发生了T/C突变;229bp和166bp杂和切开;166bp纯合未切开,代表基因序列中含有限制酶切位点,未发生了T/C突变;所得基因型符合Hardy-Weinberg平衡。②mtDNA16189T/C变异在2型糖尿病患者中占32.26%,在对照组中占15.24%,差异有显著性(P<0.05)。③2型糖尿病患者中mtDNA16189T/C变异组HomA值(13.26±13.47)高于非变异组(5.97±9.47),差异有显著性(P<0.05)。④2型糖尿病中mtDNA16189T/C变异组和非变异组在空腹血糖、空腹C-肽、餐后2hC-肽、诊断年龄、病程、体质量指数、血脂、微量蛋白尿、糖化血红蛋白差异无显著性(t=-1.17～2.01,P=0.04～0.84)。结论:尚不能认为线粒体基因16189T/C变异引起胰岛素分泌功能下降,但该基因突变可能通过胰岛素抵抗加重2型糖尿病的发展。

AIM:To assess the prevalence rate of mitochondrial DNA(mtDNA) 16189T/C mutation in the type 2 diabetics, and study the relationship of mtDNA 16189 T/C mutation with insulin resistance and insulin secretion. METHODS:The polymerase chain reaction(PCR) and restriction fragment length polymorphism(RFLP) technology were used to examine the mtDNA 16189T/C mutation in 155 type 2 diabetics(study group),who were hospitalized in the Second Hospital of Jilin University,and 162 non-diabetics,who were hospitalized in the Department of Surgery of the Second Hospital of Jilin University at the same period and the spouse of some cases(normal control group),the general condition and part of the metabolic indexes were compared between the two groups. RESULTS:①Three mtNDA 16189 genotypes were obtained:229 bp was homozygous and not cut open,no restriction site was observed in the representative gene ranking,there was T/C mutation;229 bp and 166 bp were heterogyzous and cut open;166 bp was homozygous and not cut open,restriction site was observed in the representative gene ranking, there was no T/C mutation;all the genotypes were corresponded with the Hardy-Wemberg balance regulation.②The prevalence rate of mtNDA 16189 T/C mutation in the type 2 diabetic group(32.26%) was significantly higher than that in the control group(15.24%)(P< 0.05).③Among the type 2 diabetics,the HomA value in the mtNDA 16189 T/C mutation group(13.26±13.47) was significantly higher than that in the non-mutation group(5.97±9.47)(P< 0.05).④There were no significant differences in the levels of fasting plasma glucose and C-peptide, postprandial 2-hour C-peptide,diagnostic age,disease course,body mass index,serum lipid level,microalbuminuria and glycosylated hemoglobin between the mtNDA 16189 T/C mutation group and the non-mutation group in the type 2 diabetics(P=0.04 to 0.84). CONCLUSION:The descent of insulin secretion should not be considered to be the result of mtDNA 16189 mutation in type 2 diabetics,which accelerates the development of type 2 diabetes through insulin resistance.