Hinohara Kunihiko, Nakajima Toshiaki, Yasunami Michio, Houda Shigeru, Sasaoka Taishi, Yamamoto Ken, Lee Bok-Soo, Shibata Hiroki, Tanaka-Takahashi Yumiko, Takahashi Megumi, Arimura Takuro, Sato Akinori, Naruse Taeko, Ban Jimin, Inoko Hidetoshi, Yamada Yoshiji, Sawabe Motoji, Park Jeong-Euy, Izumi Toru, Kimura Akinori
Department of Molecular Pathogenesis, Medical Research Institute, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo-ku, Tokyo 113-8510, Japan.
Hum Genet. 2009 Oct;126(4):539-47. doi: 10.1007/s00439-009-0698-6. Epub 2009 Jun 10.
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.
冠状动脉疾病（CAD）基于冠状动脉粥样硬化，可能表现为心肌梗死或心绞痛。尽管人们普遍认为遗传因素与CAD有关，并且已经报道了一些与疾病相关的基因，但只有少数基因能够被重复验证，这表明可能存在其他与CAD相关的基因。为了确定CAD的新型易感基因座，我们在筛选中使用了微卫星标记，并发现了六个不同的候选CAD基因座。随后的单核苷酸多态性（SNP）关联研究揭示了CAD与巨核母细胞白血病因子-1基因（MKL1）之间的关联。在日本人群中发现了MKL1启动子SNP -184C>T与CAD的关联，并且在另一个日本人群和韩国人群中得到了重复验证。对MKL1启动子SNP的功能分析表明，较高的MKL1表达与CAD相关。这些发现表明MKL1参与了CAD的发病机制。
