两个携带线粒体tRNAMet/tRNAGlnA4401G和tRNACysG5821A突变的中国汉族原发性高血压家系的临床及分子遗传学特征

doi:10.3724/SP.J.1005.2014.0127

遗传 ›› 2014, Vol. 36 ›› Issue (2): 127-134.doi: 10.3724/SP.J.1005.2014.0127

两个携带线粒体tRNAMet/tRNAGlnA4401G和tRNACysG5821A突变的中国汉族原发性高血压家系的临床及分子遗传学特征

许美芬^1,2, 何轶群^1,2, 耿军伟^1,2, 孟燕子^1,2, 于涵^1,2, 林枝^1,2, 施苏雪^1,2, 薛凌^1,2, 卢中秋³, 管敏鑫^1,2,4

1. 温州医科大学检验医学院、生命科学学院, 温州 325035;
2. 温州医科大学浙江省医学遗传学重点实验室, 温州 325035;
3. 温州医科大学附属第一医院急诊科, 温州 325000;
4. 浙江大学遗传研究所, 杭州 310023

收稿日期:2013-09-16 修回日期:2013-11-12 出版日期:2014-02-20 发布日期:2014-01-25
作者简介:许美芬, 在读硕士研究生, 专业方向：医学遗传学。Tel: 0577-86689905; E-mail: xu11004080@163.com
基金资助:
国家自然科学基金项目(编号：81070794, 30971600), 国家青年科学基金项目(编号：31100903), 浙江省自然科学基金项目(编号：Y2110399), 温州市瓯海区科技计划项目(编号：2011XM047), 温州市瓯海区科技局社会发展科学研究项目(编号：20120177)和浙江省大学生科技创新活动计划(新苗人才计划)项目(编号：2013R413045)资助

The mitochondrial tRNAMet/tRNAGlnA4401G and tRNACysG5821A mutations may be associated with hypertension in two Han Chinese families

Meifen Xu^1,2, Yiqun He^1,2, Junwei Geng^1,2, Yanzi Meng^1,2, Han Yu^1,2, Zhi Lin^1,2, Suxue Shi^1,2, Ling Xue^1,2, Zhongqiu Lu³, Minxin Guan^1,2,4

1. School of Laboratory Medicine and Life Science, Wenzhou Medical University, Wenzhou 325035, China;
2. Zhejiang Provincial Key Laboratory of Medical Genetics, Wenzhou Medical University, Wenzhou 325035, China;
3. Emergercy Department, the First Affiliated Hospital of Wenzhou Medical University, Wenzhou 325000, China;
4. Institute of Genetics, Zhejiang University, Hangzhou 310023, China

Received:2013-09-16 Revised:2013-11-12 Published:2014-02-20 Online:2014-01-25

摘要/Abstract

摘要：

线粒体tRNA基因可能是原发性高血压发病相关的突变热点区域。文章报道了两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。家系先证者和其他成员的临床数据表明, 家系中母系成员高血压发病的严重程度存在差异, 发病年龄也从36~79岁不等。对两个家系先证者使用24对有部分重叠的引物进行线粒体DNA全序列扩增分析, 结果发现这两个先证者均携带同质性的tRNAMet/tRNAGlnA4401G和tRNACysG5821A突变, 多态性变异位点都属于东亚单体型C。A4401G突变可能通过影响tRNAMet和tRNAGln前体的加工引起线粒体tRNA代谢水平的改变, 而tRNACysG5821A突变位于tRNACys氨基酸受体臂, 该突变使tRNACys氨基酸受体臂上原有的G6-C67配对消失, 可能影响tRNACys空间结构和功能的稳定性, 致使线粒体功能障碍。因此, tRNAMet/tRNAGlnA4401G和tRNACysG5821A突变可能是这两个原发性高血压家系的分子致病基础。

关键词: 原发性高血压, 线粒体DNA, 突变, 单体型

Abstract:

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.

Key words: essential hypertension, mitochondrial DNA, mutation, haplotype

许美芬, 何轶群, 耿军伟, 孟燕子, 于涵, 林枝, 施苏雪, 薛凌, 卢中秋, 管敏鑫. 两个携带线粒体tRNAMet/tRNAGlnA4401G和tRNACysG5821A突变的中国汉族原发性高血压家系的临床及分子遗传学特征[J]. 遗传, 2014, 36(2): 127-134.

Meifen Xu, Yiqun He, Junwei Geng, Yanzi Meng, Han Yu, Zhi Lin, Suxue Shi, Ling Xue, Zhongqiu Lu, Minxin Guan. The mitochondrial tRNAMet/tRNAGlnA4401G and tRNACysG5821A mutations may be associated with hypertension in two Han Chinese families[J]. HEREDITAS, 2014, 36(2): 127-134.

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两个携带线粒体tRNAMet/tRNAGlnA4401G和tRNACysG5821A突变的中国汉族原发性高血压家系的临床及分子遗传学特征

The mitochondrial tRNAMet/tRNAGlnA4401G and tRNACysG5821A mutations may be associated with hypertension in two Han Chinese families

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