Associations of variations in the MRF2/ARID5B gene with susceptibility to type 2 diabetes in the Japanese population

Abstract

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.

Relationship between Modulator Recognition Factor 2/AT-rich Interaction Domain 5B Gene Variations and Type 2 Diabetes Mellitus or Lipid Metabolism in a Northern Chinese Population

“…The four variants were also associated with higher HbA1c and FPG levels. [11] In the present study, participants who harbored the MRF2/ARID5B rs10740055AA genotype had a higher incidence of T2DM, and the risk of T2DM was also increased in subjects harboring the T allele of rs10761600, consistent with the results of the previous study. The rs10740055 and rs10761600 SNPs thus appear to be common loci for T2DM susceptibility among Asian populations.…”

“…[1112] However, the relationships between these four SNPs and T2DM have only been reported in a Japanese population.…”

Population Genomics Reveal Recent Speciation and Rapid Evolutionary Adaptation in Polar Bears

“…Regulation of EHD3 plays a role in a molecular pathway related to heart failure (Gudmundsson et al, 2012). ARID5B is involved in pathogenesis of atherosclerosis and adipogenesis (Wang et al, 2012). ABCC6 is associated with transport of molecules across membranes and is associated with premature atherosclerosis (Trip et al, 2002), and CUL7 plays a role in vascular morphogenesis (Arai et al, 2003).…”

Knockdown of AT-rich interaction domain (ARID) 5B gene expression induced AMPKα2 activation in cardiac myocytes

“…Similarly, the expression of multiple adipogenic genes was inhibited following transient transfection of siRNA targeting ARID5B in 3T3-L1 cells (14). Since a role of ARID5B in the regulation of metabolism has been suggested (11)(12)(13), we investigated the potential involvement of ARID5B and AMP-activated protein kinase (AMPK) in the metabolism of cardiac myocytes.…”

“…Important roles of ARID5B in growth, immune, and sexual development have been suggested (10). While the role of ARID5B in cancer is still elusive, previous studies suggested that genetic variations in the ARID5B gene are associated with susceptibility to coronary atherosclerosis or type 2 diabetes in Japanese populations (11,12).…”