Association of a 5178C→A (Leu237Met) polymorphism in the mitochondrial DNA with a low prevalence of myocardial infarction in Japanese individuals
Association of a 5178C→A (Leu237Met) polymorphism in the mitochondrial DNA with a low prevalence of myocardial infarction in Japanese individuals
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DOI：
10.1016/j.atherosclerosis.2004.03.008
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发表时间：
2004-08-01
期刊：
影响因子：
5.3
通讯作者：
Tanaka, M
中科院分区：
文献类型：
--
作者：
Takagi, K;Yamada, Y;Tanaka, M
由于线粒体是细胞中活性氧（ROS）的主要来源，线粒体功能的某些改变可导致血管内皮细胞和平滑肌细胞中的代谢紊乱，从而导致血管功能障碍。我们以前证明，在线粒体DNA（mtDNA）的核苷酸5178的NADH脱氢酶亚基2（ND 2）基因，这导致在氨基酸237 Leu -> Met取代的C -> A颠换，被发现在日本百岁老人比对照组更频繁。我们还证明了Mt5178 C--> A多态性在糖尿病受试者中具有抗动脉粥样硬化作用。我们在病例对照研究中检测了线粒体ND 2基因Mt5178 C--> A（Leu 237 Met）多态性是否与心肌梗死（MI）的低患病率相关。采用聚合酶链反应-限制性片段长度多态性（PCR-RFLP）技术或基于比色法的等位基因特异性DNA探针技术检测ND 2基因的基因型。校正年龄、性别、体重指数、吸烟状况、高血压、糖尿病、高胆固醇血症和高尿酸血症的多变量logistic回归分析显示，对照组中Mt5178 A基因型的频率显著高于MI受试者。这些结果表明，5178 A C基因型的线粒体ND 2基因多态性是保护免受MI，这种效果将解释，至少部分地，它的贡献长寿。(C)2004爱思唯尔爱尔兰有限公司保留所有权利。
Because mitochondria are the major sources of reactive oxygen species (ROS) in cells, certain alterations in mitochondrial functions can lead to metabolic perturbation in vascular endothelial cells and smooth muscle cells, resulting in vascular dysfunction. We previously demonstrated that a C --> A transversion in mitochondrial DNA (mtDNA) at nucleotide 5178 of the NADH dehydrogenase subunit 2 (ND2) gene, which results in a Leu --> Met substitution at amino acid 237, was found more frequently in Japanese centenarians than in controls. We also demonstrated that this Mt5178C --> A polymorphism has anti-atherosclerotic effects in diabetic subjects. We have now examined whether the Mt5178C --> A (Leu237Met) polymorphism in the mitochondrial ND2 gene is associated with a low prevalence of myocardial infarction (MI) in a case-control study. The genotype of ND2 gene was determined either with a polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) or a colorimetry-based allele-specific DNA probe assay. Multivariate logistic regression analysis with adjustment for age, gender, body mass index, smoking status, hypertension, diabetes mellitus, hypercholesterolemia, and hyperuricemia revealed - that the frequency of the Mt5178A genotype was significantly higher in controls than in subjects with MI. These results suggest that the 5178A C Genotype of mitochondrial ND2 gene polymorphism is protective against MI; and this effect would explain, at least in part, its contribution to longevity. (C) 2004 Elsevier Ireland Ltd. All rights reserved.