PPARγ Pro12Ala Pro/Pro and resistin SNP-420 G/G genotypes are synergistically associated with plasma resistin in the Japanese general population

Objective The Ala allele of the Pro12Ala polymorphism (rs1801282) of peroxisome proliferator-activated receptor gamma (PPAR gamma) is protective against type 2 diabetes (T2DM). Resistin, secreted from adipocytes, causes insulin resistance in rodents. Resistin gene expression is reduced by the PPAR gamma ligand. We previously reported that subjects with the G/G genotype of a resistin gene single nucleotide polymorphism (SNP) at -420 (rs1862513) had the highest circulating resistin levels, followed by C/G and C/C. The aim of this study was to determine the relationship among PPAR gamma Pro12Ala polymorphism, resistin SNP-420, and plasma resistin. Design, patients and measurements We cross-sectionally analysed 2077 community-dwelling subjects attending an annual medical check-up. Genotypes were determined by TaqMan analysis. Fasting plasma resistin was measured using ELISA. Results Plasma resistin appeared to be higher in subjects with the Pro/Pro genotype of PPAR gamma than those with Pro/Ala and Ala/Ala genotypes (mean +/- SE, 11 center dot 6 +/- 0 center dot 2 vs. 10 center dot 4 +/- 0 center dot 5 mu g/l). Multiple regression analysis, adjusted for age, gender, BMI, and resistin SNP-420, revealed that the Pro/Pro genotype was a positive predictor of plasma resistin (PPAR gamma , Pro/Pro vs. Pro/Ala + Ala/Ala, unstandardized regression coefficient (beta) = 1 center dot 03, P = 0 center dot 0384). The effects of the Pro/Pro genotype of PPAR gamma (Pro/Pro vs. Pro/Ala + Ala/Ala) and the G/G genotype of resistin SNP-420 (G/G vs. C/C) on plasma resistin were synergistic (beta = 4 center dot 76, P = 0 center dot 011). Conclusions The PPAR gamma Pro12Ala Pro/Pro and resistin SNP-420 G/G genotypes were synergistically associated with plasma resistin, when adjusted for age, gender, and BMI, in the Japanese general population.