Xu Yunhong, Chen Ximing, Huang Huanliang, Liu Wanting
Department of Cardiology, The Third Affiliated Hospital of Guangzhou Medical University.
Int Heart J. 2017 Feb 7;58(1):95-99. doi: 10.1536/ihj.16-205. Epub 2017 Jan 20.
Mutations in mitochondrial DNA are associated with the pathogenesis of essential hypertension. We report here the clinical, genetic, and molecular characterization of a three-generation Han Chinese family with essential hypertension. Most strikingly, this family exhibited a high penetrance of essential hypertension. Sequence analysis of the mitochondrial genome showed the presence of a homoplasmic T5655C mutation in tRNA, together with the A4401G mutation in the adjacent region between tRNA and tRNA. Notably, the T5655C mutation was localized at the acceptor arm of tRNA, disrupted the high conserved base-pairing (1A-72T), and may impair the tRNA function. Moreover, the A4401G mutation was reported to decrease the steady-state level of tRNA and tRNA, and consequently caused the mitochondrial dysfunction responsible for hypertension. Taken together, the combination of T5655C and A4401G mutations in mitochondrial tRNA genes may account for the high penetrance and expressivity of hypertension in this Chinese family. Thus, our findings may provide new insight into the pathogenesis of this disorder.
线粒体DNA突变与原发性高血压的发病机制相关。我们在此报告一个三代汉族原发性高血压家系的临床、遗传和分子特征。最显著的是，这个家系表现出原发性高血压的高外显率。线粒体基因组序列分析显示，在tRNA中存在同质性T5655C突变，以及在tRNA和tRNA之间的相邻区域存在A4401G突变。值得注意的是，T5655C突变位于tRNA的受体臂，破坏了高度保守的碱基配对（1A - 72T），可能损害tRNA功能。此外，据报道A4401G突变会降低tRNA和tRNA的稳态水平，从而导致导致高血压的线粒体功能障碍。综上所述，线粒体tRNA基因中T5655C和A4401G突变的组合可能解释了这个中国家系中高血压的高外显率和表现度。因此，我们的发现可能为该疾病的发病机制提供新的见解。
