Interaction of genetic risk factors confers increased risk for metabolic syndrome: the role of peroxisome proliferator-activated receptor γ

Božina, Tamara and Sertić, Jadranka and Lovrić, Jasna and Jelaković, Bojan and Šimić, Iveta and Reiner, Željko (2014) Interaction of genetic risk factors confers increased risk for metabolic syndrome: the role of peroxisome proliferator-activated receptor γ. Genetic Testing and Molecular Biomarkers, 18 (1). pp. 32-40. ISSN 1945-0265

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Abstract

AIM: The aim of the study was to estimate the influence of interactions between peroxisome proliferator-activated receptor γ (PPARγ) and target genes lipoprotein lipase (LPL), interleukin 6 (IL6), angiotensin converting enzyme (ACE), and angiotensin II type 1 receptor (AT1R) on metabolic syndrome (MetSy) and its traits. ----- METHODS: The study included 527 participants (263 with MetSy and 264 controls). Genotyping of PPARγ Pro12Ala, LPL PvuII (-/+), IL6 -174G>C, ACE I/D and AT1R 1166A>C was performed using polymerase chain reaction-restriction fragment length polymorphism-based methods. ----- RESULTS: Interaction between PPARγ Pro12Ala and LPL Pvu(-/+) improved prediction of MetSy over and above prediction based on a model containing no interactions (χ(2)=7.22; df=1; p=0.007). In the group of participants with PPARγ Pro12Ala or Ala12Ala genotypes, those with the LPL Pvu (-/+) or (+/+) genotype had greater odds for MetSy (odds ratio OR=5.98; 95% confidence interval CI: 1.46-24.47, p=0.013). Interaction between PPARγ Pro12Ala and IL6 -174G>C improved prediction of high fasting blood glucose (χ(2)=13.99; df=1; p<0.001). PPARγ Ala12 variant was found protective in patients with IL6 -174GG genotype (OR=0.10; 95% CI: 0.02-0.57, p=0.01), while in the case of IL6 -174C allele carriers, for PPARγ Ala12 carriers, larger odds for high glucose levels compared with Pro12 variant were observed (OR=2.39; 95% CI: 1.11-5.17, p=0.026). Interactions of PPARγ and ACE were significant for BMI. In the group with ACE DD genotype, those with PPARγ Pro12Ala or Ala12Ala genotype have greater odds for obesity (OR=9.98; 95% CI: 1.18-84.14, p=0.034). ----- CONCLUSIONS: PPARγ gene variants can, in interaction with some of its target genes, modulate physiological processes leading to the development of MetSy.

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