Maternally inherited hypertension is associated with the mitochondrial tRNAIle A4295G mutation in a Chinese family
Maternally inherited hypertension is associated with the mitochondrial tRNAIle A4295G mutation in a Chinese family
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DOI：
10.1016/j.bbrc.2007.12.150
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发表时间：
2008-03-21
影响因子：
3.1
通讯作者：
Guan, Min-Xin
中科院分区：
文献类型：
--
作者：
Li, Zongbin;Liu, Yuqi;Guan, Min-Xin
线粒体DNA的突变与心血管疾病有关。我们在此报告一个三代母系遗传性高血压汉族家系的临床、遗传和分子特征。该家系所有母系亲属均表现出不同程度的高血压，发病年龄为36 ~ 56岁。该家系完整线粒体DNA的序列分析显示存在已知的高血压相关tRNA（Ile）A4295 G突变和33个其他变体，属于亚洲单倍群D4 j。A4295 G突变，从细菌到人线粒体都非常保守，位于反密码子的3'端，对应于tRNA（Ile）的常规位置37。A4295 G突变在几个遗传无关的心血管疾病家系中的发生，但没有242名中国对照，强烈表明该突变参与心血管疾病的发病机制。在其他变体中，tRNA（Glu）A14693 G和ND 1 G11696 A突变与其他线粒体疾病相关。A14693 G突变是tRNA（Glu）的TPsi C环上高度保守的核苷，其对tRNA的结构和功能具有重要意义。此外，ND 4 G11696 A突变与Leber遗传性视神经病变相关。因此，tRNA（Ile）基因A4295 G突变与ND 4基因G11696 A突变和tRNA（Glu）基因A14693 G突变的结合可能是该家系高血压发病率的原因。(c)2007年爱思唯尔公司All rights reserved.
Mutations in mitochondrial DNA have been associated with cardiovascular disease. We report here the clinical, genetic, and molecular characterization of one three-generation Han Chinese family with maternally transmitted hypertension. All matrilineal relatives in this family exhibited the variable degree of hypertension at the age at onset of 36 to 56 years old. Sequence analysis of the complete mitochondrial DNA in this pedigree revealed the presence of the known hypertension-associated tRNA(Ile) A4295G mutation and 33 other variants, belonging to the Asian haplogroup D4j. The A4295G mutation, which is extraordinarily conserved from bacteria to human mitochondria, is located at immediately 3' end to the anticodon, corresponding to conventional position 37 of tRNA(Ile). The occurrence of the A4295G mutation in several genetically unrelated pedigrees affected by cardiovascular disease but the absence of 242 Chinese controls strongly indicates that this mutation is involved in the pathogenesis of cardiovascular disease. Of other variants, the tRNA(Glu) A14693G and ND1 G11696A mutations were implicated to be associated with other mitochondrial disorders. The A14693G mutation, which is a highly conserved nucleoside at the T Psi C-loop of tRNA(Glu), has been implicated to be important for tRNA structure and function. Furthermore, the ND4 G11696A mutation was associated with Leber's hereditary optic neuropathy. Therefore, the combination of the A4295G mutation in the tRNA(Ile) gene with the ND4 G11696A mutation and tRNA(Glu) A14693G mutation may contribute to the high penetrance of hypertension in this Chinese family. (c) 2007 Elsevier Inc. All rights reserved.