Li Haiying, Geng Junwei, Yu Han, Tang Xiaowen, Yang Xiangjun, Xue Ling
Department of Cardiology, First Affiliated Hospital of Soochow University, Suzhou, Jiangsu 215006, China; Department of Cardiology, First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang 325000, China.
Attardi Institute of Mitochondrial Biomedicine, School of Laboratory Medicine and Life Sciences, Wenzhou Medical University, Wenzhou, Zhejiang 325035, China.
Biochem Biophys Res Commun. 2018 Jan 1;495(1):574-581. doi: 10.1016/j.bbrc.2017.11.061. Epub 2017 Nov 10.
Mitochondrial DNA mutations are one of the molecular genetic bases of hypertension. Here, we performed clinical, genetic and mutational evaluation, molecular characterization as well as biochemical analysis of a Chinese Han family with maternally inherited hypertension. The m.15909A > G variant in tRNA was identified. This mutation abolished a highly conserved base pairing (11U-24A) in the D-stem of tRNA and affected the structure and function of mitochondrial tRNA. As a result, the overall levels of mitochondrial translation products was decreased. The reduced mitochondrial protein synthesis resulted in the decrease in the activity of complex, and in turn, the production of ATP decreased and the generation of ROS increased. The m.15909A > G mutation maybe an inherited factor leading to the development of hypertension in this Chinese Han pedigree.
线粒体DNA突变是高血压的分子遗传基础之一。在此，我们对一个患有母系遗传高血压的中国汉族家庭进行了临床、遗传和突变评估、分子特征分析以及生化分析。在tRNA中鉴定出了m.15909A>G变异。该突变消除了tRNA D茎中一个高度保守的碱基对（11U-24A），并影响了线粒体tRNA的结构和功能。结果，线粒体翻译产物的总体水平降低。线粒体蛋白质合成减少导致复合物活性降低，进而ATP生成减少，ROS生成增加。m.15909A>G突变可能是导致这个中国汉族家系高血压发生的一个遗传因素。
