中国汉族原发性高血压患者线粒体tRNAMet基因突变

摘要

为探讨线粒体tRNAMet基因突变与中国汉族人原发性高血压发生发展之间的关系,文章收集990名原发性高血压患者一般资料(性别、年龄、发病年龄、体重指数、家族遗传史等)、血常规、血生化及心脏彩色超声检查结果;采集入选者的静脉血,分离并提取白细胞中的DNA,PCR扩增线粒体tRNAMet,纯化后测序.以发生tRNAMet突变的原发性高血压患者为指示病例,匹配8例未发生突变的原发性高血压患者为对照病例,统计分析指示病例和对照病例在血常规、血生化及心脏彩色超声检查等方面的异同.结果显示在990名原发性高血压患者中,有8名患者发生线粒体tRNAMet突变,突变分布在6个位点,分别为A4401G、C4410A、U4418C、A4435G、U4454C和C4456U.与对照病例相比,指示病例的平均发病时间显著提前,这种早发现象与体重指数无关.指示病例高密度脂蛋白胆固醇的平均值明显高于对照病例;血红蛋白平均值明显低于对照病例:舒张末期左室内径、每搏输出量、和心脏指数平均值等明显高于对照病例,射血分数平均值低于对照病例.在指示病例中,有5名患者有高血压母系遗传史,1名患者具有父系遗传史,2名患者否认有家族遗传史.以上研究结果提示线粒体tRNAMet突变可能会导致其结构和功能的变化,进而通过干扰血脂代谢、血细胞的稳态以及心脏的结构与功能,参与了原发性高血压的发生和发展.%The objective of the present study was to explore the relationship between mitochondrial tRNAMet mutation and development of essential hypertension in Chinese Han individuals.A total of 990 patients with essential hypertension were involved.The general data (sex, age, body mass index, onset age, and family history) and information on routine blood test,blood biochemical examination, and color Doppler echocardiography of these patients were collected.A11 subjects underwent venous blood drawing for seperating white blood cells and DNA extraction.Then, mitochondrial tRNAMet was amplified and sequenced after purification.The patients who carried the tRNAMet mutation were taken as the indicative cases and the controls were the patients with essential hypertension who did not carry the mutation.We performed a comparative analysis on the routine blood test, blood biochemical examination, color Doppler echocardiography, and other data between the indicative cases and control cases.Among the 990 essential hypertensive patients, there were 8 who carried the tRNAMet mutation, and 6 mutation sites were confirmed, including A440IG, C44IOA, U4418C, A4435G U4454C, and C4456U.Compared with the control cases, the indicative cases developed essential hypertension at earlier ages.The average levels of high density of lipoprotein cholesterol, left ventricular end diastolic diameter, stroke volume, and cardiac index were highein the indicative cases than in the controls.While the average levels of hemoglobin and left ventricular ejection fraction were lower in the indicative cases than in the control cases.Among the 8 indicative cases, 5 had maternally inherited hypertension; one had patemally inherited hypertension; and two denied any family history of hypertension.These results indicated that the mitochondrial tRNAMct mutations might induce the changes in structure and function, which was involved in the progress of the essential hypertension by disturbing the blood metabolism, the steady-state of the blood cells, and the cardiac structure and function.