Xu Meifen, He Yiqun, Geng Junwei, Meng Yanzi, Yu Han, Lin Zhi, Shi Suxue, Xue Ling, Lu Zhongqiu, Guan Minxin
School of Laboratory Medicine and Life Science, Wenzhou Medical University, Wenzhou 325035, China; Zhejiang Provincial Key Laboratory of Medical Genetics, Wenzhou Medical University, Wenzhou 325035, China.
Emergercy Department, the First Affiliated Hospital of Wenzhou Medical University, Wenzhou 325000, China.
Yi Chuan. 2014 Feb;36(2):127-34. doi: 10.3724/sp.j.1005.2014.00127.
Mitochondrial tRNA genes are the hot spots for mutations associated with essential hypertension. We report here the clinical and molecular genetic characterization of two Han Chinese pedigrees with materially inherited essential hypertension. Clinical evaluation revealed the variable severity and age-at-onset of hypertension among matrilineal relatives. In particular, the age-at-onset of hypertension in the maternal kindred ranged from 36 years to 79 years. The sequence analysis of entire mitochondrial genome in two probands showed that two probands carried the identical homoplasmic tRNAMet/tRNAGlnA4401G and tRNACysG5821A mutations and distinct sets of polymorphisms belonging to East Asian haplogroup C. The A4401G mutation may affect the processing of the precursors of tRNAMet and tRNAGln , thereby altering the tRNA metabolism. The tRNACys G5821A mutation is located in the acceptor stem of tRNACys. This mutation may abol-ish the predicted G6-C67 pairing and consequently affect the structure and stability of mitochondrial tRNACys, thereby leading to mitochondrial dysfunction. Therefore, these data suggested that the tRNAMet/tRNAGlnA4401G and tRNACys G5821A mutations are likely associated with essential hypertension in these two Chinese pedigrees.
线粒体tRNA基因是与原发性高血压相关的突变热点。我们在此报告两个母系遗传原发性高血压的汉族家系的临床和分子遗传学特征。临床评估显示母系亲属中高血压的严重程度和发病年龄各不相同。特别是，母系亲属中高血压的发病年龄在36岁至79岁之间。对两名先证者的整个线粒体基因组进行序列分析表明，两名先证者携带相同的纯合子tRNAMet/tRNAGln A4401G和tRNACys G5821A突变以及属于东亚单倍群C的不同多态性集合。A4401G突变可能影响tRNAMet和tRNAGln前体的加工，从而改变tRNA代谢。tRNACys G5821A突变位于tRNACys的接受茎。该突变可能消除预测的G6-C67配对，从而影响线粒体tRNACys的结构和稳定性，进而导致线粒体功能障碍。因此，这些数据表明tRNAMet/tRNAGln A4401G和tRNACys G5821A突变可能与这两个中国家系的原发性高血压有关。
