Genetic variations of Mrf-2/ARID5B confer risk of coronary atherosclerosis in the Japanese population.
Genetic variations of Mrf-2/ARID5B confer risk of coronary atherosclerosis in the Japanese population.
复制标题
DOI：
10.1536/ihj.49.313
复制
发表时间：
2008-05
影响因子：
1.5
通讯作者：
Guoqin Wang;Masafumi Watanabe;Y. Imai;K. Hara;I. Manabe;K. Maemura;M. Horikoshi;T. Kohro;E. Amiya;T. Sugiyama;T. Fujita;T. Kadowaki;T. Yamazaki;R. Nagai
中科院分区：
文献类型：
--
作者：
Guoqin Wang;Masafumi Watanabe;Y. Imai;K. Hara;I. Manabe;K. Maemura;M. Horikoshi;T. Kohro;E. Amiya;T. Sugiyama;T. Fujita;T. Kadowaki;T. Yamazaki;R. Nagai
平滑肌细胞（SMC）的表型改变被认为是冠状动脉疾病（CAD）等动脉粥样硬化病变发病机制的关键。Mrf-2/ARID 5 B是富含AT相互作用域的转录因子家族的成员，在心血管系统中高度表达，并被认为通过调节SMC的分化在SMC的表型改变中起重要作用。此外，最近对基因工程小鼠的研究表明，这种转录因子参与肥胖和脂肪形成，这是动脉粥样硬化发病机制的关键方面。因此，我们假设Mrf-2基因的遗传变异可能与CAD的易感性相关。我们研究了11种常见的Mrf-2基因变异，以确定它们是否与475名CAD受试者和310名对照受试者的CAD易感性相关。冠心病组与对照组相比，SNP 4的G等位基因（rs 2893880）和SNP 6的G等位基因（rs7087507）的纯合子频率显著增高（P=0.0002，rs 2893880; P=0.0058，rs7087507）。4个邻近SNP（SNP 4至SNP 7）（rs 2893880，rs 10740055，rs7087507和rs 10761600）显示几乎完全连锁不平衡，单倍型分析表明，单倍型G（rs 2893880）-C（rs 10740055）-G（rs7087507）-A（rs 10761600）与冠心病易感性呈显著负相关（P=0.049）。此外，这些负面的疾病协会仍然存在后，考虑到logistic回归分析，以消除混杂的传统冠状动脉危险因素。这些结果提示Mrf-2基因多态性可能与冠心病易感性相关。然而，需要更大规模的前瞻性研究来澄清这些发现。
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.