PPARgamma 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 (PPARgamma) is protective against type 2 diabetes (T2DM). Resistin, secreted from adipocytes, causes insulin resistance in rodents. Resistin gene expression is reduced by the PPARgamma 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 PPARgamma Pro12Ala polymorphism, resistin SNP-420, and plasma resistin.


METHODS
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 PPARgamma than those with Pro/Ala and Ala/Ala genotypes (mean +/- SE, 11.6 +/- 0.2 vs. 10.4 +/- 0.5 microg/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 (PPARgamma , Pro/Pro vs. Pro/Ala + Ala/Ala, unstandardized regression coefficient (beta) = 1.03, P = 0.0384). The effects of the Pro/Pro genotype of PPARgamma (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 = 4.76, P = 0.011).


CONCLUSIONS
The PPARgamma 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.
Osawa
Haruhiko
H
Department of Molecular and Genetic Medicine, Ehime University Graduate School of Medicine, Toon, Ehime, Japan. harosawa@m.ehime-u.ac.jp
Tabara
Yasuharu
Y
Kawamoto
Ryuichi
R
Ohashi
Jun
J
Ochi
Masaaki
M
Onuma
Hiroshi
H
Nishida
Wataru
W
Yamada
Kazuya
K
Nakura
Jun
J
Miki
Tetsuro
T
Makino
Hideichi
H
Kohara
Katsuhiko
K
D000368:Aged; D044466:Asian People / Q000235:genetics; D003430:Cross-Sectional Studies; D005260:Female; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D020125:Mutation, Missense; D047495:PPAR gamma / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D052243:Resistin / Q000097:blood* / Q000235:genetics*
D047495:PPAR gamma; D052243:Resistin