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PPARγ Pro12Ala Pro/Pro and resistin SNP-420 G/G genotypes are synergistically associated with plasma resistin in the Japanese general population |
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| Authors: | Haruhiko Osawa Yasuharu Tabara† Ryuichi Kawamoto‡ Jun Ohashi§ Masaaki Ochi Hiroshi Onuma Wataru Nishida Kazuya Yamada¶ Jun Nakura Tetsuro Miki Hideichi Makino Katsuhiko Kohara |
| Institution: | Department of Molecular and Genetic Medicine;, Department of Basic Medical Research and Education, Ehime University Graduate School of Medicine, Ehime, Japan;, Department of Internal Medicine, Seiyo-city Nomura Hospital;, Doctoral Program in Life System Medical Sciences, Graduate School of Comprehensive Human Sciences, University of Tsukuba, Ibaraki, Japan, and;Department of Health and Nutritional Science, Faculty of Human Health Science, Matsumoto University;, Department of Geriatric Medicine, Ehime University Graduate School of Medicine, Ehime, Japan |
| Abstract: | Objective The Ala allele of the Pro12Ala polymorphism (rs1801282) of peroxisome proliferator-activated receptor γ (PPARγ) is protective against type 2 diabetes (T2DM). Resistin, secreted from adipocytes, causes insulin resistance in rodents. Resistin gene expression is reduced by the PPARγ 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 PPARγ 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 PPARγ than those with Pro/Ala and Ala/Ala genotypes (mean ± SE, 11·6 ± 0·2 vs. 10·4 ± 0·5 μg/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 (PPARγ , Pro/Pro vs. Pro/Ala + Ala/Ala, unstandardized regression coefficient (β) = 1·03, P = 0·0384). The effects of the Pro/Pro genotype of PPARγ (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 (β = 4·76, P = 0·011). Conclusions The PPARγ 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. |
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