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

Aims: 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. Methods: 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). Results: 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. Conclusions: 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. © 2011 The Japan Diabetes Society.