Association of PPAR Alpha Intron 7 G/C, PPAR Gamma 2 Pro12Ala, and C161T Polymorphisms with Serum Fetuin-A Concentrations

Abstract

BACKGROUND: Both peroxisome activator proteins (PPARs) and fetuin-A play a role in lipid and glucose metabolism. AIMS: We investigated whether PPARalpha intron 7 G2468/C and PPARgamma2 Pro12Ala and PPARgamma exon 6 C161T polymorphisms are associated with serum fetuin-A concentrations. PATIENTS AND METHODS: The PPARalpha intron 7 G/C polymorphism was studied in cohort 1 (79 reference individuals, 165 postinfarction patients). The two PPARgamma polymorphisms were investigated in cohort 2 (162 reference individuals, 165 postinfarction patients). Fetuin-A levels and PPAR polymorphisms were determined by radial immunodiffusion and polymerase chain reaction-restriction fragment length polymorphism techniques. RESULTS: The C allele variant of PPARalpha intron 7 G2467C was associated with higher fetuin-A levels (p = 0.018). Postinfarction status (p = 0.001), PPARalpha intron 7 GG/GC/CC genotypes (p = 0.032), and the C allele (p = 0.021) were the strongest determinants of fetuin-A concentration in a multiple regression model. Higher fetuin-A levels were associated with the Pro variant of PPARgamma2 (p = 0.047). Postinfarction status (p = 0.041) and BMI (p < 0.001) but not PPARgamma2 Pro were the strongest determinants of fetuin-A concentrations. PPARgamma exon 6 C161T genotypes were not associated with fetuin-A levels. CONCLUSIONS: Fetuin-A was determined mainly by the PPARalpha intron 7C allele and postinfarction status in cohort 1 and the BMI and postinfarction in cohort 2. The PPARalpha intron 7C and PPARgamma2 Pro variants are associated with fetuin-A levels.