Megakaryoblastic leukemia factor-1 gene in the susceptibility to coronary artery disease
Megakaryoblastic leukemia factor-1 gene in the susceptibility to coronary artery disease
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DOI：
10.1007/s00439-009-0698-6
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发表时间：
2009-10-01
期刊：
影响因子：
5.3
通讯作者：
Kimura, Akinori
中科院分区：
文献类型：
--
作者：
Hinohara, Kunihiko;Nakajima, Toshiaki;Kimura, Akinori
冠状动脉疾病（coronary artery disease，CAD）是以冠状动脉粥样硬化为基础的疾病，可表现为心肌梗死或心绞痛。虽然遗传因素与CAD相关已被广泛接受，并且已报道了几个疾病相关基因，但只有少数可以复制，这表明可能存在其他CAD相关基因。为了确定新的CAD易感基因座，我们使用微卫星标记进行筛选，发现了6个不同的候选CAD基因座。随后的单核苷酸多态性（SNP）关联研究揭示了CAD与巨核细胞白血病因子-1基因（MKL 1）之间的关联。在日本人群中发现了与MKL 1启动子SNP（-184 C> T）的关联，并且在另一个日本人群和韩国人群中复制了该关联。MKL 1启动子SNP的功能分析表明，MKL 1的较高表达与CAD相关。这些结果表明，MKL 1参与了CAD的发病机制。
Coronary artery disease (CAD) is based on the atherosclerosis of coronary artery and may manifest with myocardial infarction or angina pectoris. Although it is widely accepted that genetic factors are linked to CAD and several disease-related genes have been reported, only a few could be replicated suggesting that there might be some other CAD-related genes. To identify novel susceptibility loci for CAD, we used microsatellite markers in the screening and found six different candidate CAD loci. Subsequent single nucleotide polymorphism (SNP) association studies revealed an association between CAD and megakaryoblastic leukemia factor-1 gene (MKL1). The association with a promoter SNP of MKL1, -184C > T, was found in a Japanese population and the association was replicated in another Japanese population and a Korean population. Functional analysis of the MKL1 promoter SNP suggested that the higher MKL1 expression was associated with CAD. These findings suggest that MKL1 is involved in the pathogenesis of CAD.