Li Zongbin, Liu Yuqi, Yang Li, Wang Shiwen, Guan Min-Xin
Institute of Geriatric Cardiology, Chinese PLA General Hospital, Beijing, China.
Biochem Biophys Res Commun. 2008 Mar 21;367(4):906-11. doi: 10.1016/j.bbrc.2007.12.150. Epub 2008 Jan 3.
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 TpsiC-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.
线粒体DNA突变与心血管疾病有关。我们在此报告一个三代汉族母系遗传高血压家族的临床、遗传和分子特征。该家族中所有母系亲属在36至56岁发病时均表现出不同程度的高血压。对这个家系的完整线粒体DNA进行序列分析，发现存在已知的与高血压相关的tRNA（Ile）A4295G突变以及其他33个变异，属于亚洲单倍群D4j。A4295G突变从细菌到人类线粒体都高度保守，位于反密码子紧邻的3'端，对应于tRNA（Ile）的常规位置37。在几个患有心血管疾病的无亲缘关系家系中出现A4295G突变，但在242名中国对照中未发现，这强烈表明该突变参与了心血管疾病的发病机制。在其他变异中，tRNA（Glu）A14693G和ND1 G11696A突变被认为与其他线粒体疾病有关。A14693G突变是tRNA（Glu）TψC环上一个高度保守的核苷，被认为对tRNA的结构和功能很重要。此外，ND4 G11696A突变与Leber遗传性视神经病变有关。因此，tRNA（Ile）基因中的A4295G突变与ND4 G11696A突变和tRNA（Glu）A14693G突变的组合可能导致了这个中国家族中高血压的高外显率。
