Mitochondrial tRNA variants in Chinese subjects with coronary heart disease.
Mitochondrial tRNA variants in Chinese subjects with coronary heart disease.
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DOI：
10.1161/jaha.113.000437
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发表时间：
2014-01-27
影响因子：
5.4
通讯作者：
Guan MX
中科院分区：
文献类型：
--
作者：
Qin Y;Xue L;Jiang P;Xu M;He Y;Shi S;Huang Y;He J;Mo JQ;Guan MX
冠心病是世界范围内导致死亡的主要原因。线粒体遗传决定因素的发展，这种疾病仍然较少探索。我们对80名汉族冠心病患者和4个冠心病家族的125名成员以及512名中国对照者进行了22个线粒体tRNA基因的临床和遗传评估和突变筛查。该分析确定了9个tRNA基因中16个核苷酸的变化。其中，T5592C突变在tRNAGln受体茎上建立了高度保守的碱基配对（5G‐68C），而G15927A突变破坏了tRNAThr反密码子茎上高度保守的碱基配对（28C‐42G）。然而，其他tRNA变体是多态性。携带T5592C突变的BJH24家系、携带G15927A突变的BJH15家系和BJH45家系显示出冠心病的母系遗传。线粒体基因组序列分析显示，这些家族的所有母系亲属均存在T5592C或G15927A突变，但没有其他功能上显著的突变。我们之前的观察表明，这些mtDNA突变导致trna结构的改变导致线粒体功能障碍。这可能是mtDNA突变增加冠心病风险的第一个证据。我们的发现可能为这种疾病的病理生理学提供新的见解。
Coronary heart disease is the leading cause of death worldwide. Mitochondrial genetic determinants for the development of this disorder remain less explored. We performed a clinical and genetic evaluation and mutational screening of 22 mitochondrial tRNA genes in a cohort of 80 genetically unrelated Han Chinese subjects and 125 members of 4 families with coronary heart disease and 512 Chinese control subjects. This analysis identified 16 nucleotide changes among 9 tRNA genes. Of these, the T5592C mutation creates a highly conservative base pairing (5G‐68C) on the acceptor stem of tRNAGln, whereas the G15927A mutation destabilizes a highly conserved base pairing (28C‐42G) in the anticodon stem of tRNAThr. However, the other tRNA variants were polymorphisms. The pedigrees of BJH24 carrying the T5592C mutation, BJH15, and BJH45 harboring the G15927A mutation exhibited maternal transmission of coronary heart disease. Sequence analysis of their mitochondrial genomes revealed the presence of T5592C or G15927A mutation but the absence of other functionally significant mutations in all matrilineal relatives of these families. Our previous observations showed that altered structures of tRNAs by these mtDNA mutations caused mitochondrial dysfunction. These may be the first evidence that mtDNA mutations increase the risk of coronary heart disease. Our findings may provide new insights into the pathophysiology of this disorder.