Abstract
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.
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Acknowledgments
We are grateful Dr. Gen Tamiya for his help in the MS analysis and Dr. Akihiko Hamamatsu for the preparation of coronary artery sections. This work was supported in part by Grant-in-Aids for Scientific Research from the Ministry of Education, Culture, Sports, Science and Technology (MEXT) of Japan, a research grant from the Ministry of Health, Labour and Welfare, Japan, research grants for Japan-Korea collaboration research from Japan Society for the Promotion of Science and by a KOSEF grant, the Korea-Japan Basic Scientific Cooperation Program.
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Supplementary Figure S1 Results of the genome-wide screening: P values by Fisher’s exact test based on 2 × 2 contingency tables (green line) or on 2 × m contingency tables (blue line) for the first screening as well as 2 × 2 contingency tables (pink line) or on 2 × m contingency tables (purple line) for the second screening are shown. Yellow circles indicate 42 MS that showed significant associations in both the first and second screenings and tested in the following confirmation analysis by individual ty**. Red arrows indicate 6 MS that showed significant associations in the third screening
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Hinohara, K., Nakajima, T., Yasunami, M. et al. Megakaryoblastic leukemia factor-1 gene in the susceptibility to coronary artery disease. Hum Genet 126, 539–547 (2009). https://doi.org/10.1007/s00439-009-0698-6
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DOI: https://doi.org/10.1007/s00439-009-0698-6