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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
Author(s) -
Osawa Haruhiko,
Tabara Yasuharu,
Kawamoto Ryuichi,
Ohashi Jun,
Ochi Masaaki,
Onuma Hiroshi,
Nishida Wataru,
Yamada Kazuya,
Nakura Jun,
Miki Tetsuro,
Makino Hideichi,
Kohara Katsuhiko
Publication year - 2009
Publication title -
clinical endocrinology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.055
H-Index - 147
eISSN - 1365-2265
pISSN - 0300-0664
DOI - 10.1111/j.1365-2265.2008.03465.x
Subject(s) - resistin , medicine , endocrinology , genotype , single nucleotide polymorphism , snp , type 2 diabetes , polymorphism (computer science) , peroxisome proliferator activated receptor , allele , insulin resistance , biology , diabetes mellitus , receptor , adiponectin , gene , genetics
Summary 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.