Department of Cardiovascular Medicine, Graduate School of Medicine, University of Tokyo, Tokyo, Japan.
J Hum Genet. 2012 Nov 26;57(11):727-33. doi: 10.1038/jhg.2012.101. Epub 2012 Sep 13.
Modulator recognition factor-2 (Mrf2/AT-rich interaction domain (Arid)5b) has been revealed to be involved in pathogenesis of atherosclerosis and adipogenesis. Single-nucleotide polymorphisms (SNPs) in the MRF2/ARID5B gene are associated with coronary artery disease (CAD) and has been proposed as a candidate gene for type 2 diabetes (T2D). The study was aimed to determine whether any of the four MRF2/ARID5B SNPs (rs2893880, rs10740055, rs7087507 and rs10761600) associated with susceptibility to CAD are also associated with T2D, and to determine whether SNP genotype influences the levels of adiponectin and other clinical factors. Association of MRF2/ARID5B SNPs was investigated in 500 diabetic patients from the Department of Metabolic Diseases at the University of Tokyo and 243 hospital-based nondiabetic individuals from the Institute for Adult Disease Asahi Life Foundation Hospital and 500 community-based nondiabetic individuals from the Hiroshima Atomic Bomb Casualty Council Health Management Center. Associations of haplotypes of these SNP with levels of adiponectin and other clinical factors were evaluated when the data was available. We found rs2893880C, rs10740055A, rs7087507A and rs10761600T were increasingly associated with T2D in terms of allele/genotype frequencies of each SNP and their haplotype combinations. Individuals with haplotype CAAT indicated an 1.86 times higher prevalence of diabetes compared with individuals with GCGA (OR 1.86 (95% confidence interval (CI) 1.43-2.41)). Furthermore, CAAT significantly associated with adiponectin levels and other clinical factors. In conclusion, polymorphisms on the MRF2/ARID5B gene were associated with susceptibility to T2D as well as adiponectin and other clinical factors, which was in a completely concordant way with their associations with CAD.
调节剂识别因子-2(Mrf2/富含 AT 的相互作用域(Arid)5b)已被揭示参与动脉粥样硬化和脂肪生成的发病机制。MRF2/ARID5B 基因中的单核苷酸多态性(SNP)与冠心病(CAD)相关,并已被提议作为 2 型糖尿病(T2D)的候选基因。本研究旨在确定与 CAD 易感性相关的四个 MRF2/ARID5B SNP(rs2893880、rs10740055、rs7087507 和 rs10761600)中是否有任何一个也与 T2D 相关,并确定 SNP 基因型是否影响脂联素和其他临床因素的水平。在东京大学代谢疾病科的 500 名糖尿病患者和朝日生命基金会成人疾病研究所的 243 名基于医院的非糖尿病个体以及广岛原子爆炸受害者健康管理中心的 500 名基于社区的非糖尿病个体中,研究了 MRF2/ARID5B SNP 的相关性。当数据可用时,评估了这些 SNP 的单倍型与脂联素和其他临床因素水平的关系。我们发现,在每个 SNP 的等位基因/基因型频率及其单倍型组合方面,rs2893880C、rs10740055A、rs7087507A 和 rs10761600T 与 T2D 的相关性逐渐增加。与 GCGA 相比,携带 CAAT 单倍型的个体糖尿病患病率高 1.86 倍(OR 1.86(95%置信区间(CI)1.43-2.41))。此外,CAAT 与脂联素水平和其他临床因素显著相关。总之,MRF2/ARID5B 基因的多态性与 T2D 易感性以及脂联素和其他临床因素相关,这与它们与 CAD 的相关性完全一致。