Genetic Variations of Mrf-2/Arid5b Confer Risk of Coronary Atherosclerosis in the Japanese Population
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概要
- 論文の詳細を見る
A phenotypic change of smooth muscle cells (SMCs) is considered to be critical in the pathogenesis of atherosclerotic lesions such as coronary artery disease (CAD). Mrf-2/ARID5B, a member of the AT-rich interaction domain family of transcription factors, is highly expressed in the cardiovascular system and is believed to play essential roles in the phenotypic change of SMCs through its regulation of SMC differentiation. In addition, recent studies on gene-engineered mice suggested that this transcriptional factor is involved in obesity and adipogenesis, which are critical aspects for the pathogenesis of atherosclerosis. Thus, we hypothesized that genetic variations of the Mrf-2 gene might be associated with susceptibility to CAD. We investigated 11 common genetic variations of Mrf-2 to determine whether they were associated with susceptibility to CAD in 475 CAD subjects and 310 control subjects. The prevalence of homozygotes for the minor allele G of SNP4 (rs2893880) and minor allele G of SNP6 (rs7087507) were significantly more frequent in the control subjects than in patients with CAD (P = 0.0002, rs2893880, P = 0.0058, rs7087507). Four nearby SNPs (SNP4 to SNP7) (rs2893880, rs10740055, rs7087507 and rs10761600) showed almost complete linkage disequilibrium, and haplotype analysis revealed that the haplotype G (rs2893880)-C (rs10740055)-G (rs7087507)-A (rs10761600) was also significantly negatively associated with susceptibility to CAD (P = 0.049). Moreover, these negative disease associations still existed after logistic regression analysis was taken into account to eliminate confounding conventional coronary risk factors. The results implicate possible disease relevance of the polymorphisms in the Mrf-2 gene with susceptibility to CAD. However, a larger scale prospective study is needed to clarify these findings.
- インターナショナル・ハート・ジャーナル刊行会の論文
著者
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NAGAI Ryozo
Department of Cardiovascular Medicine, University of Tokyo
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Kadowaki Takashi
Department of Health Science, Shiga University of Medical Science
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Imai Yasushi
Department of Cardiovascular Medicine, Graduate School of Medicine, The University of Tokyo
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Yamazaki Tsutomu
Department of Clinical Epidemiology & Systems, The University of Tokyo
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Kohro Takahide
Department of Translational Research for Healthcare and Clinical Science, The University of Tokyo
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Kohro Takahide
Department Of Cardiology Tokyo University School Of Medicine
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Wang Guoqin
Department of Cardiovascular Medicine, The University of Tokyo
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Watanabe Masafumi
Department of Cardiovascular Medicine, The University of Tokyo
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Manabe Ichiro
Department of Cardiovascular Medicine, The University of Tokyo
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Maemura Koji
Department of Cardiovascular Medicine, The University of Tokyo
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Sugiyama Takao
Institute for Adult Diseases, Asahi Life Foundation
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Imai Yasushi
Department Of Cardiovascular Medicine Graduate School Of Medicine The University Of Tokyo
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Wang Guoqin
Department Of Cardiovascular Medicine The University Of Tokyo
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Sugiyama Takao
東京大学 医学系研究科循環器内科
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Hara Kazuo
Departments of Diabetes and Metabolism, Graduate School of Medicine, the University of Tokyo
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Horikoshi Momoko
Departments of Diabetes and Metabolism, Graduate School of Medicine, the University of Tokyo
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Amiya Eisuke
Departments of Cardiovascular Medicine, Graduate School of Medicine, the University of Tokyo
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Fujita Takeshi
Hitachi, Ltd., Central Research Laboratory
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Amiya Eisuke
Department Of Cardiovascular Medicine University Of Tokyo
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Manabe Ichiro
Department Of Caldiology University Of Tokyo
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Sugiyama Takao
Institute For Adult Disease Asahi Life Foundation
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Maemura Koji
Department Of Cardiovascular Medicine Course Of Medical And Dental Sciences Graduate School Of Biome
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Watanabe Masafumi
Department Of Cardiovascular Medicine Graduate School Of Medicine The University Of Tokyo
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Hara Kazuo
Department Of Clinical Bioinformatics Graduate School Of Medicine University Of Tokyo
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Yamazaki Tsutomu
Department Of Applied Chemistry Graduate School Of Engineering Tokyo University Of Agriculture And T
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Nagai Ryozo
Department Cardiovascular Medicine The University Of Tokyo Hospital
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Kadowaki Takashi
Department Of Cardiology Kawasaki Medical School
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HORIKOSHI Momoko
Department of Diabetes and Metabolism, Graduate School of Medicine, the University of Tokyo
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Wang Guoqin
Departments of Cardiovascular Medicine, Graduate School of Medicine, the University of Tokyo
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Manabe Ichiro
Departments of Cardiovascular Medicine, Graduate School of Medicine, the University of Tokyo
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Kohro Takahide
Departments of Translational Research for Healthcare and Clinical Science, Graduate School of Medicine, the University of Tokyo
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Maemura Koji
Departments of Cardiovascular Medicine, Graduate School of Medicine, the University of Tokyo
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Kadowaki Takashi
Departments of Diabetes and Metabolism, Graduate School of Medicine, the University of Tokyo
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