线粒体DNA U4b单倍群:中国塔吉克族高原原发性高血压的遗传易感因素  

MtDNA haplogroup U4b is a genetic susceptibility factor for high altitude essential hypertension in the Chinese Tajik population

作　　者：陈郁 高亮 龚亮 陈兴书 阳盛洪 罗勇军 CHEN Yu;GAO Liang;GONG Liang;CHEN Xing-shu;YANG Sheng-hong;LUO Yong-jun(Department of Military Medical Geography,Army Health Service Training Base,Army Medical University,Chongqing 400038;The 950th Hospital of PLA,Yecheng 844900;The 949th Hospital of PLA,Aletai 836300,China)

机构地区：[1]陆军军医大学陆军卫勤训练基地军事医学地理学教研室,重庆400038 [2]解放军第950医院,新疆叶城844900 [3]解放军第949医院,新疆阿勒泰836300

出　　处：《中国应用生理学杂志》2021年第3期225-229,共5页Chinese Journal of Applied Physiology

基　　金：国家自然科学基金面上项目(81571843);全军后勤科研计划重点课题(BLJ18J005);陆军军医大学科技创新能力提升专项项目(2019XYY09);青海省基础研究计划项目(2018-ZJ-705);科技部第二次青藏高原综合科学考察研究专题(2019QZKK0607)。

摘　　要：目的:探讨线粒体DNA变异与中国塔吉克族高原原发性高血压的关系。方法:在中国塔吉克族人群中,收集了53例高原原发性高血压病例和46例正常对照。通过PCR扩增线粒体DNA片段,经测序拼接获得线粒体全基因组,与剑桥序列比对以筛选线粒体DNA变异,分析在病例组与对照组中的分布差异,采用生物信息学工具预测阳性相关变异的功能。结果:与对照组相比,U4b单倍群在病例组的频率显著升高(P=0.023,OR=7.062,CI(95%)=1.306-38.182),该单倍群内的8个变异位点也存在显著性差异(P均<0.05)。其中,线粒体DNA 15693T>C位点是位于线粒体细胞色素b基因编码区的唯一错义变异,使得第316位氨基酸由蛋氨酸改变为苏氨酸;生物信息学分析表明,该变异可能通过影响蛋白的二级结构发挥生物学功能。结论:线粒体DNA U4b单倍群是中国塔吉克族人群高原原发性高血压的遗传易感因素,线粒体DNA 15693T>C突变可能是高原原发性高血压的重要分子机制。Objective:To investigate the relationship between mitochondrial DNA(mtDNA)variation and high altitude essential hypertension(HAEH)in the Chinese Tajik population.Methods:Fifty-three patients with HAEH and 46 healthy subjects were enrolled from the Chinese Tajik population.The mtDNA fragments were amplificated by polymerase chain reaction,and products were sequenced to acquire full sequence of mtDNA.The mtDNA sequences of all subjects were compared to the Cambridge sequence to explore mtDNA variations and analyze difference between HAEH and healthy controls.Online softwares were applied to predict function changes caused by positive associated mtDNA variations.Results:Compared to the control group,the frequency of haplogroup U4b was significant higher in HAEH group(P=0.023,OR=7.062,CI(95%)=1.306-38.182),and the frequencies of 8 mutations from haplogroup U4b showed a significant difference between the HAEH group and control group(all with P values below 0.05).The mt DNA15693T>C mutation was the only missense mutation,which affected amino acid 316 in mitochondrial cytochrome b(MTCYB)by changing it from methionine to threonine.Bioinformatics analysis indicated that the mutation in MTCYB may play a biological role through affecting the second structure of protein.Conclusion:MtDNA subhaplogroup U4b is a genetic factor for HAEH in the Chinese Tajik population,and mtDNA15693T>C mutation may be an important molecular mechanism of HAEH.

关 键 词：高原 高血压 线粒体DNA 塔吉克族 

分 类 号：R544.1[医药卫生—心血管疾病]