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

Bernadett Márkus,László Kalabay,Dorina Supák,Krisztián Vörös,Károly Cseh,Zsolt Melczer

doi:10.1155/2017/7636019

Abstract

Background Both peroxisome activator proteins (PPARs) and fetuin-A play a role in lipid and glucose metabolism. Aims We investigated whether PPARα intron 7 G2468/C and PPARγ2 Pro12Ala and PPARγ exon 6 C161T polymorphisms are associated with serum fetuin-A concentrations. Patients and Methods The PPARα intron 7 G/C polymorphism was studied in cohort 1 (79 reference individuals, 165 postinfarction patients). The two PPARγ 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 PPARα intron 7 G2467C was associated with higher fetuin-A levels (p = 0.018). Postinfarction status (p = 0.001), PPARα 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 PPARγ2 (p = 0.047). Postinfarction status (p = 0.041) and BMI (p < 0.001) but not PPARγ2 Pro were the strongest determinants of fetuin-A concentrations. PPARγ exon 6 C161T genotypes were not associated with fetuin-A levels. Conclusions Fetuin-A was determined mainly by the PPARα intron 7C allele and postinfarction status in cohort 1 and the BMI and postinfarction in cohort 2. The PPARα intron 7C and PPARγ2 Pro variants are associated with fetuin-A levels.

Highlights

Human fetuin-A is a multifunctional hepatic glycoprotein that has been involved in the development of obesity [1,2,3], insulin resistance [4], metabolic syndrome [1, 5], type 2 diabetes [6,7,8], adipocyte dysfunction [9], and fatty liver [4].Peroxisome proliferator-activated receptors (PPARs) are members of the nuclear hormone receptor superfamily of ligand-activated transcription factors
We aimed to investigate whether polymorphisms of PPARγ (PPARγ2 Pro12Ala and exon 6 C161T) and PPARα are associated with or may affect serum fetuin-A levels in two cohorts
Postinfarction patients, had a significantly higher T allele frequency of the PPARγ C161T compared to reference subjects

Summary

Introduction

Human fetuin-A is a multifunctional hepatic glycoprotein that has been involved in the development of obesity [1,2,3], insulin resistance [4], metabolic syndrome [1, 5], type 2 diabetes [6,7,8], adipocyte dysfunction [9], and fatty liver [4].Peroxisome proliferator-activated receptors (PPARs) are members of the nuclear hormone receptor superfamily of ligand-activated transcription factors. The T allele of the PPARγ exon 6 C161T polymorphism was supposed to have protective role against coronary artery disease in Chinese population [16], whereas others found that this allele was associated with an increased Both peroxisome activator proteins (PPARs) and fetuin-A play a role in lipid and glucose metabolism. We investigated whether PPARα intron 7 G2468/C and PPARγ2 Pro12Ala and PPARγ exon 6 C161T polymorphisms are associated with serum fetuin-A concentrations. The C allele variant of PPARα intron 7 G2467C was associated with higher fetuin-A levels (p = 0.018). Postinfarction status (p = 0.001), PPARα 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. The PPARα intron 7C and PPARγ2 Pro variants are associated with fetuin-A levels

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