苏中地区母系遗传性高血压病患者线粒体DNA 3777～4679区域基因突变相关研究

The mitochondrial DNA 3777-4679 region gene mutations in maternally inherited essential hypertensive individuals in central district of Jiangsu province in China

目的：探讨苏中地区母系遗传性高血压病（MIEH）患者发病与线粒体DNA（mtDNA）突变的关系。方法实验分为研究组和对照组。收集300例MIEH患者作为研究组，调查发病年龄、进行超声心动图检查。选择同期体检证实的300例健康人群作为对照组。抽取受试者外周静脉血，对序列3777～4679位置的mtDNA进行直接基因测序，通过与标准人类mtDNA序列的剑桥序列进行对比，分析正常人群与MIEH 患者mtDNA突变情况；根据mtDNA有无突变，对发病年龄和超声心动图资料进行对比分析。结果（1）与正常人群相比，突变集中在一些呼吸链NADH氧化还原酶亚单位1（ND1）、NADH氧化还原酶亚单位2（ND2），高突变位点为ND1C3970T突变。（2）MIEH中mtDNA突变者发病年龄明显低于非突变者（P＜0.05），并且突变者舒张末期左心室内径（LVIDd）、收缩末期左心室内径（LVIDs）平均值明显高于无突变者（P＜0.05）；左心室射血分数（LVEF）平均值低于无突变者（P＜0.05）。结论 mtDNA结构改变可以导致其相应功能异常，进而影响心脏靶器官结构和功能，参与MIEH的发生和发展。

Objective To explore the relationship between mitochondrial DNA （mtDNA） variations and development of maternally inherited essential hypertension （MIEH） in central district of Jiangsu province in China. Methods Samples used in this study were extracted from 300 cases of MIEH, who met the diagnostic standard of MIEH, and 300 cases of normotensives （NT）. Genomic DNA was isolated from whole blood cells of all the participants. The hottest spots of hypertension were screened using oligodeoxynucleotides 3777-4679 purified and subsequently analyzed by direct sequencing according to the revised consensus cambridge sequence. The frequency, density, type and evolution conservative of mtDNA variations were comprehensively analyzed. Clinic data included age of onset and color Doppler echocardiography of the patients with MIEH were collected. Then, we performed a comparative analysis on the age of onset and echocardiography data between the patients with and without the mtDNA mutation. Results （1） MIEH patients had more mtDNA variations in frequency and density than NT. The mtDNA variations were in regions of ND1, ND2 binding site and high mutation site was ND1C3970T. （2） Among MIEH patients, the mutation cases developed essential hypertension at earlier ages than the cases who did not carry the mutation （P〈0.05）;the average levels of left ventricular internal dimension in diastole（LVIDd） and left ventricular internal dimension in systole stroke volume（LVIDs） were higher in the mutation cases than the cases who did not carry the mutation（P〈0.05）, while the average levels of left ventricular ejection fraction（LVEF） were lower than the latter one（P〈0.05）. Conclusion Our present results indicated that the mtDNA mutations might induce the changes in structure and function of the corresponding mitochondrion, which may be involved in the progress of maternal transmission of hypertension through disturbing cardiac structure and function.