A single-nucleotide polymorphism in the human THADA gene is associated with circulating resistin in the general Japanese population

Ryoichi Kawamura1, Yasuharu Tabara2,3, Hiroshi Onuma1,3, Ryuichi Kawamoto4,3, Jun Ohashi5, Yasunori Takata1,3, Wataru Nishida1,3, Katsuhiko Kohara6,3, Hideichi Makino7, Tetsuro Miki6,3, Haruhiko Osawa1,3
1Department of Molecular and Genetic Medicine, Ehime University Graduate School of Medicine, Toon, Japan
2Department of Basic Medical Research and Education, Ehime University Graduate School of Medicine, Toon, Japan
3Ehime Proteo-Medicine Research Center, Ehime University, Toon, Japan
4Department of Community Medicine, Ehime University Graduate School of Medicine, Toon, Japan
5Doctoral Program in Life System Medical Sciences, Graduate School of Comprehensive Human Sciences, University of Tsukuba, Tsukuba, Japan
6Department of Geriatric Medicine, Ehime University Graduate School of Medicine, Toon, Japan
7Shiraishi Hospital Diabetes Center, Imabari, Japan

Tóm tắt

Resistin, secreted from adipocytes, causes insulin resistance in mice. We previously reported that the G/G genotype of a single-nucleotide polymorphism (SNP)-420 (rs1862513) in the human resistin gene (RETN) resulted in an increase in circulating resistin and susceptibility to type 2 diabetes (T2D). Whereas PPARG Pro12Ala Pro/Pro and RETN SNP-420 G/G genotypes were synergistically associated with plasma resistin, no other trans-acting SNPs associated with circulating resistin have been reported. We cross-sectionally analyzed the association between plasma resistin and SNPs recently reported to be associated with T2D in 2,038 community-dwelling Japanese individuals. These SNPs are located around the TCF7L2, KCNJ11, IGF2BP2, CDKN2A/B, SLC30A8, CDKAL1, GCKR, HHEX, KCNQ1, WFS1, TCF2, TSPAN8, CDC123, ADAMTS9, THADA, JAZF1, PANK1, IRS1, HK1, and MTNR1B genes. The SNPs were analyzed by TaqMan assays, and plasma resistin was determined by ensyme-linked immunosorbent assay (ELISA). Plasma resistin was significantly associated with rs7578597 in THADA [C/C 6.81, C/T 8.64 ± 5.26, T/T 11.54 ± 6.54 ng/ml; P = 0.0159, analysis of variance (ANOVA)]. Plasma resistin appeared to be higher in individuals with the THADA T/T and RETN SNP-420 G/G genotypes. A multiple regression analysis revealed that plasma resistin was also associated with THADA after adjustment for age, gender, body mass index, and SNP-420 (β = 1.89, P = 0.036). A nominal association between plasma resistin and rs4607103 in ADAMTS9 disappeared after multivariate adjustment. Circulating resistin was associated with rs7578597 in THADA in the general Japanese population. In addition to the cis-acting effect of SNP-420 in the RETN promoter, circulating resistin could be affected by other trans-acting SNPs.

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