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.
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Acknowledgements
This study was supported in part by a Grant-in-Aid from the Ministry of Education, Culture, Sports, Science and Technology (MEXT), Japan (to RN), and a research grant from the National Institute of Biomedical Innovation, Japan (to RN); The study was also supported in part by Special Coordination Funds for Promoting Science and Technology by MEXT, Japan (to TY and RN) and the Japan Society for the Promotion of Science (JSPS) through its Funding Program for World-Leading Innovative R&D on Science and Technology (FIRST Program). We thank Yuki Itoh, Eri Fujiu, Chika Masuo, Yasuko Kubono and Yukino Sato for their technical assistance. We also thank Robert E Brandt (Founder and CEO, MedEd, Japan) for editing the manuscript.
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Wang, G., Watanabe, M., Imai, Y. et al. Associations of variations in the MRF2/ARID5B gene with susceptibility to type 2 diabetes in the Japanese population. J Hum Genet 57, 727–733 (2012). https://doi.org/10.1038/jhg.2012.101
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DOI: https://doi.org/10.1038/jhg.2012.101
