title: Genetic variations of Mrf-2/ARID5B confer risk of coronary atherosclerosis in the Japanese population.
abstract: 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.
authors.affiliation: Department of Cardiovascular Medicine, Graduate School of Medicine, the University of Tokyo, Bunkyo-ky, Tokyo, Japan.
authors.forename: Guoqin
authors.initials: G
authors.lastname: Wang
authors.forename: Masafumi
authors.initials: M
authors.lastname: Watanabe
authors.forename: Yasushi
authors.initials: Y
authors.lastname: Imai
authors.forename: Kazuo
authors.initials: K
authors.lastname: Hara
authors.forename: Ichiro
authors.initials: I
authors.lastname: Manabe
authors.forename: Koji
authors.initials: K
authors.lastname: Maemura
authors.forename: Momoko
authors.initials: M
authors.lastname: Horikoshi
authors.forename: Takahide
authors.initials: T
authors.lastname: Kohro
authors.forename: Eisuke
authors.initials: E
authors.lastname: Amiya
authors.forename: Takao
authors.initials: T
authors.lastname: Sugiyama
authors.forename: Takeshi
authors.initials: T
authors.lastname: Fujita
authors.forename: Takashi
authors.initials: T
authors.lastname: Kadowaki
authors.forename: Tsutomu
authors.initials: T
authors.lastname: Yamazaki
authors.forename: Ryozo
authors.initials: R
authors.lastname: Nagai
mesh_terms: D000368:Aged; D000818:Animals; D016022:Case-Control Studies; D003324:Coronary Artery Disease / Q000235:genetics*; D004268:DNA-Binding Proteins / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease; D006720:Homozygote; D006801:Humans; D007564:Japan; D008297:Male; D051379:Mice; D008875:Middle Aged; D032389:Myocytes, Smooth Muscle / Q000378:metabolism*; D020641:Polymorphism, Single Nucleotide; D012307:Risk Factors; D014157:Transcription Factors / Q000235:genetics*
chemical_list: C503805:ARID5B protein, human; D004268:DNA-Binding Proteins; D014157:Transcription Factors