论文部分内容阅读
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 This article reports the clinical and molecular genetic characteristics of a Han Chinese family with hypertension and maternally inherited characteristics. The mitochondrial genes of maternal members and normal controls were amplified by polymerase chain reaction (PCR), and the mutations were screened and correlated by data alignment. Results The prevalence of hypertension was high in this pedigree. In addition, the complete mitochondrial genome analysis of maternal members showed that there was a homogenous tRNA ~ (Thr) T15941C mutation and ND1C3497T mutation, and the T15941C mutation was located in the tRNA ~ (Thr) gene T_ψC loop highly conserved base 61, mutation disrupted the original 57A-61T base pairing, bioinformatics software analysis also found that T15941C mutation changes tRNA ~ (Thr) secondary structure, may cause mitochondria tRNA metabolic disorder. Conclusion Mitochondrial tRNA ~ (Thr) T15941C and ND1C3497T mutations may be the essential molecular basis for the pathogenesis of this family with hypertension. The phenotypic differences in mitochondrial DNA homogeneity and age of onset revealed that the nuclear, environmental and mitochondrial genetic backgrounds may have some influence on the phenotype of tRNA ~ (Thr) T15941C mutation.