原发性高血压相关的线粒体tRNA突变研究  

The study of mitochondrial tRNA mutations associated with essential hypertension

作　　者：余雪姣 金菊仙 董全胜 陈秀花[1] Yu Xuejiao

机构地区：[1]浙江省衢州市人民医院,324000 [2]中国人民解放军94981部队卫生队,江西南昌330200

出　　处：《浙江临床医学》2020年第6期791-792,798,共3页Zhejiang Clinical Medical Journal

基　　金：浙江省衢州市科技资助项目(2016075)。

摘　　要：目的探讨线粒体tRNA基因突变和原发性高血压发生发展之间的关系,为原发性高血压的早期诊断和治疗提供理论依据。方法PCR扩增200例原发性高血压患者和100例正常对照样本线粒体tRNA基因组并测序,测序结果与线粒体标准序列进行比对,鉴定突变位点,并用种系进化保守分析对候选的突变位点进行致病性验证,评估原发性高血压和线粒体tRNA突变的相关性。结果PCR-Sanger测序后发现3个突变:线粒体tRNAMet A 4435G、tRNAGln T 4363C和tRNALys A 8343G突变,而这些突变在正常对照中均未发现。此外,A4435G、T4363C和A8343G突变位于进化上高度保守的区域,可能引起线粒体tRNA代谢障碍,进而线粒体蛋白合成受阻,引起线粒体功能损伤。结论线粒体tRNAMet A4435G、tRNAGln T4363C、tRNALys A8343G突变和原发性高血压有关,为原发性高血压的早期诊断和干预提供理论依据。Objective To explore the potential association between mt-tRNA mutations and essential hypertension,and provide valuable information for early diagnosis and treatment for essential hypertension.Methods The mt-tRNA genes of 200 patients with hypertension and 100 controls were amplified by PCR,moreover,the PCR products were sequenced and compared with the standard sequences of mitochondrial genome to detect the mutations,the phylogenetic approach were further utilized to evaluate the pathogenic status of mt-tRNA mutations,and the association between hypertension and mt-tRNA mutations were assessed.Results PCR-Sanger sequence were identified three mutations:mt-tRNAMet A4435G,tRNAGln T4363C and tRNALys A8343G,while these mutations were not detected in controls.In addition,these mutations were localized at the highly conserved nucleotides of the corresponding tRNA and may cause the failure in tRNA metabolism,subsequently caused the mitochondrial protein synthesis defects,and led to mitochondrial dysfunction that was responsible for hypertension.Conclusion Mt-tRNAMet A4435G,tRNAGln T4363C and tRNALys A8343G mutations may be associated with hypertension,thus,our study provides novel insight into the early diagnosis and clinical prevention of mitochondrial hypertension.

关 键 词：高血压 mt-tRNA突变 衢州地区 

分 类 号：R73[医药卫生—肿瘤]