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
通讯作者: 管敏鑫, 教授, 博士生导师, 研究方向：人类遗传学和线粒体疾病。E-mail: gminxin88@gmail.com E-mail:gminxin88@gmail.com
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 Online:2014-02-20 Published: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.

参考文献

[1] Chalmers J, MacMahon S, Mancia G, Whitworth J, Beilin L, Hansson L, Neal B, Rodgers A, Ni Mhurchu C, Clark T. 1999 World Health Organization-International Society of Hypertension Guidelines for the management of hyperten-sion. Guidelines sub-committee of the World Health Or-ganization. Clin Exp Hypertens, 1999, 21(5?6): 1009?1060. <\p>

[2] Gu D, Reynolds K, Wu X, Chen J, Duan X, Muntner P, Huang G, Reynolds RF, Su S, Whelton PK, He J. Prevalence, awareness, treatment, and control of hyperten¬sion in China. Hypertension, 2002, 40(6): 920–927. <\p>

[3] 李宗斌, 刘昱圻, 李彦华, 陈瑞, 王琳, 朱庆磊, 李泱, 王士雯. 中国汉族原发性高血压患者线粒体tRNAMet基因突变. 遗传, 2011, 33(6): 601–606. <\p>

[4] Fuentes RM, Notkola IL, Shemeikka S, Tuomilehto J, Nissinen A. Familial aggregation of blood pressure: a population-based family study in eastern Finland. J Hum Hypertens, 2000, 14(7): 441–445. <\p>

[5] Wang S, Li R, Fettermann A, Li Z, Qian Y, Liu Y, Wang X, Zhou A, Mo JQ, Yang L, Jiang P, Taschner A, Rossmanith W, Guan MX. Maternally inherited essential hypertension is associated with the novel 4263A>G mutation in the mi-tochondrial tRNAIle gene in a large Han Chinese family. Circ Res, 2011, 108(7): 862–870. <\p>

[6] Wilson FH, Hariri A, Farhi A, Zhao HY, Petersen KF, Toka HR, Nelson-Williams C, Raja KM, Kashgarian M, Shul- man GI, Scheinman SJ, Lifton RP. A cluster of metabolic defects caused by mutation in a mitochondrial tRNA. Science, 2004, 306(5699): 1190–1194. <\p>

[7] Merante F, Myint T, Tein I, Benson L, Robinson BH. An additional mitochondrial tRNA(Ile) point mutation (A-to-G at nucleotide 4295) causing hypertrophic cardiomyopathy. Hum Mutat, 1996, 8(3): 216–222. <\p>

[8] Li RH, Liu YQ, Li ZB, Yang L, Wang SW, Guan MX. Failures in mitochondrial tRNAMet and tRNAGln metabolism caused by the novel 4401A>G mutation are involved in essential hypertension in a Han Chinese Family. Hypertension, 2009, 54(2): 329–337. <\p>

[9] Liu YQ, Li RH, Li ZB, Wang XJ, Yang L, Wang SW, Guan MX. Mitochondrial transfer RNAMet4435A>G mutation is associated with maternally inherited hypertension in a Chinese pedigree. Hypertension, 2009, 53(6): 1083–1090. <\p>

[10] Li R, Greinwald JH Jr, Yang L, Choo DI, Wenstrup RJ, Guan MX. Molecular analysis of the mitochondrial 12S rRNA and tRNASer(UCN)genes in paediatric subjects with non-syndromic hearing loss. J Med Genet, 2004, 41(8): 615–620. <\p>

[11] Rieder MJ, Taylor SL, Tobe VO, Nickerson DA. Automating the identification of DNA variations using quality based fluorescence re-sequencing: analysis of the human mitochondrial genome. Nucleic Acids Res, 1998, 26(4): 967–973. <\p>

[12] Andrews RM, Kubacka I, Chinnery PF, Lightowlers RN, Turnbull DM, Howell N. Reanalysis and revision of the Cambridge reference sequence for human mitochondrial DNA. Nat Genet, 1999, 23(2): 147. <\p>

[13] Ruiz-Pesini E, Wallace DC. Evidence for adaptive selection acting on the tRNA and rRNA genes of human mitochondrial DNA. Hum Mutat, 2006, 27(11): 1072–1081. <\p>

[14] Lu JX, Li ZY, Zhu Y, Yang AF, Li RH, Zheng J, Cai Q, Peng GH, Zheng WW, Tang XW, Chen BB, Chen JF, Liao ZS, Yang L, Li YY, You JY, Ding Y, Yu H, Wang JD, SunDM, Zhao JY, Xue L, Wang JY, Guan MX. Mitochondrial 12S rRNA variants in 1642 Han Chinese pediatric subjects with aminoglycoside-induced and nonsyndromic hearing loss. Mitochondrion, 2010, 10(4): 380–390. <\p>

[15] Kong QP, Bandelt HJ, Sun C, Yao YG, Salas A, Achilli A, Wang CY, Zhong L, Zhu CL, Wu SF, Torroni A, Zhang YP. Updating the East Asian mtDNA phylogeny: a prerequisite for the identification of pathogenic mutations. Hum Mol Genet, 2006, 15(13): 2076–2086. <\p>

[16] 薛凌, 陈红, 孟燕子, 王燕, 卢中秋, 吕建新, 管敏鑫. 高血压相关的线粒体DNA突变. 遗传, 2011, 33(9): 911–918. <

编辑推荐

Metrics

www.chinagene.cn
备案号：京ICP备09063187号-4
总访问:,今日访问:,当前在线:

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

PDF (PC)

可视化

摘要/Abstract

引用本文

使用本文

参考文献

相关文章 15

编辑推荐

Metrics

[1]	宋睿嘉, 韩露, 孙海峰, 沈彬. 线粒体DNA碱基编辑技术研究进展[J]. 遗传, 2023, 45(8): 632-642.
[2]	李凯伦, 卢荆奥, 陈小辉, 张文清, 刘伟. 尿囊素促进破骨细胞缺陷斑马鱼骨折修复[J]. 遗传, 2023, 45(4): 341-353.
[3]	龚一鸣, 王翔宇, 贺小云, 刘玉芳, 余平, 储明星, 狄冉. 绵羊FecB突变对BMPR1B活性及BMP/SMAD通路的影响研究进展[J]. 遗传, 2023, 45(4): 295-305.
[4]	马捷, 黄露杰, 张巧霞, 朱艳, 钱露. 以A2型短指(趾)症为案例的医学遗传学PBL教学设计[J]. 遗传, 2023, 45(2): 176-183.
[5]	李璐阳, 刘孙强, 施云, 赵成程, 周红文, 郑旭琴. 一例葡萄糖激酶基因突变致低血糖症的诊疗及家系遗传分析[J]. 遗传, 2022, 44(9): 810-818.
[6]	张充, 魏子璇, 王敏, 陈瑶生, 何祖勇. 利用CRISPR/Cas9在人类黑色素瘤细胞中编辑MC1R与功能分析[J]. 遗传, 2022, 44(7): 581-590.
[7]	宋绍征, 何正义, 成勇, 于宝利, 张婷, 李丹. TALENs介导MSTN基因突变山羊的制备及性能分析[J]. 遗传, 2022, 44(6): 531-542.
[8]	王思琪, 陈阳, 罗宽宏, 史宁杰, 肖康丽, 崔振海, 曾天舒, 黎慧清. 一例SOX10基因缺失所致的Waardenburg综合征2型合并低促性腺激素性性腺功能减退症的诊断和基因检测分析[J]. 遗传, 2022, 44(12): 1158-1166.
[9]	宋青青, 张素素, 张振, 孙嘉, 杨锐, 李佶桐, 陈宏. 一例CYP11B基因突变导致11β-羟化酶缺乏症的诊疗和基因检测分析[J]. 遗传, 2022, 44(12): 1175-1182.
[10]	贾觉睿智, 肖诚, 刘艺文, 李冉, 张化冰, 于淼. 二例GCK基因突变致先天性高胰岛素性低血糖症的诊疗和基因检测分析[J]. 遗传, 2022, 44(11): 1056-1062.
[11]	肖诚, 刘洁颖, 杨春如, 于淼. LMNA基因突变相关脂肪萎缩综合征的研究进展[J]. 遗传, 2022, 44(10): 913-925.
[12]	蒋琬姿, 张丽雯, 贺彩红, 阮梅花, 季勇, 于建荣, 周红文. 家族性高胆固醇血症研究进展[J]. 遗传, 2021, 43(11): 1011-1022.
[13]	刘志勇, 任贺, 陈冲, 张京晶, 张晓梦, 石妍, 石林玉, 陈滢, 程凤, 贾莉, 陈曼, 范庆炜, 张家榕, 李万婷, 王萌春, 任子林, 刘雅诚, 倪铭, 孙宏钰, 严江伟. 基于有限突变模型和大规模数据的19个常染色体STR的实际突变率研究[J]. 遗传, 2021, 43(10): 949-961.
[14]	赵利楠, 王娜, 杨国良, 苏现斌, 韩泽广. 基于单细胞靶向测序探究基因碱基突变的方法[J]. 遗传, 2020, 42(7): 703-712.
[15]	程苗苗, 曹延延. NMD逃逸机制及其在疾病治疗中的应用[J]. 遗传, 2020, 42(4): 354-362.