线粒体tRNA^(Thr) T15941C突变位点与原发性高血压的相关性  

Association between mitochondrial tRNA^(Thr) T15941C mutation and essential hypertension

作　　者：丁禹[1,2] 高贝贝[2,3] 朱侯勇 童国新[2,3] 周亮[2,3] 叶显华[2,3] 黄进宇[2,3] 

机构地区：[1]杭州市第一人民医院中心实验室,浙江杭州310006 [2]南京医科大学附属杭州医院中心实验室 [3]杭州市第一人民医院心内科 [4]浙江中医药大学研究生院

出　　处：《中华高血压杂志》2017年第2期163-168,共6页Chinese Journal of Hypertension

基　　金：浙江省科技发展计划(2016C33207);浙江省自然科学基金(Y15H020003)

摘　　要：目的探讨线粒体DNA突变和原发性高血压的相关性。方法本文报道一个具有母系遗传特征的中国汉族原发性高血压家系的临床和分子遗传学特征。使用聚合酶链反应(PCR)扩增母系成员和正常对照的线粒体基因,经过数据比对筛选突变并进行相关分析。结果该家系的高血压发病率较高,此外,母系成员的线粒体基因全序列分析结果显示,存在同质性的tRNA^(Thr) T15941C的突变以及ND1C3497T突变,T15941C突变位于tRNA^(Thr)基因T_ψC环上高度保守的61号碱基,突变破坏了原有的57A-61T的碱基配对,生物信息学软件分析也发现T15941C突变改变了tRNA^(Thr)的二级结构,可能会引起线粒体tRNA代谢障碍。结论线粒体tRNA^(Thr) T15941C和ND1C3497T突变可能是这个原发性高血压家系发病的重要分子基础。该家系表现出的线粒体DNA同质性突变,发病年龄等表型差异,提示核基因、环境因素和线粒体遗传背景等可能对tRNA^(Thr) T15941C突变的表型表达有一定的影响。Objective To investigate the relationship between mitochondrial DNA mutations and essential hypertension. Methods The clinical,genetic and molecular characterization of a Han Chinese family with maternally inherited essential hypertension was reported. Polymerase chain reaction（PCR）amplification was used for the mitochondrial genome in matrilineal members and healthy controls,and then the mitochondrial mutations were screened and other related analyses were performed. Results This family exhibited a high penetrance of essential hypertension.In addition,sequence analysis for the complete mitochondrial genome in patients with hypertension showed the presence of the novel tRNAThr T15941C and ND1C3497T mutations. The T15941C mutation was localized at the highly-conserved nucleotide（position 61）in the TψC loop of tRNAThr,which disrupted the conserved base-pairing（57A-61T）and may cause a failure in tRNA metabolism. Moreover,through the application of bioinformatics tool,we found that the T15941 Cmutation altered the secondary structure of tRNAThr. Conclusions The combination of tRNAThr T15941C and the ND1C3497T mutations may be responsible for the essential hypertension in this Chinese family. The homoplasmic form,different age at-onset indicated that nuclear genes,environmental factors and mitochondrial genetic background may influence the clinical expression of tRNAThr T15941C mutation in this Chinese family.

关 键 词：原发性高血压 线粒体突变 tRNA代谢 中国家系 

分 类 号：R544.11[医药卫生—心血管疾病]