Association of Peroxisome Proliferator-Activated Receptor γ Polymorphisms and Haplotypes with Essential Hypertension

Abstract

Peroxisome proliferator-activated receptor γ (PPARγ) is a nuclear receptor involved in the regulation of several biochemical pathways. Blood pressure-lowering effects have been found in PPARγ agonists in several hypertensive models. The biology and research data related to the gene suggest that it could play a role in essential hypertension (EH) susceptibility. This study aimed to investigate the association between PPARγ polymorphisms and EH. About 820 subjects were genotyped for the three single-nucleotide polymorphisms used as genetic markers for the PPARγ genes (C681G, Prol2Ala, and C1431T). After correction for age, sex, smoking, alcohol consumption, body mass index, waist circumference, and fasting glucose, the G allele (CG+GG) of C681G was significantly associated with the increase in the risk of EH (odds ratio [OR]=1.54, 95%confidence interval [CI]: 1.14-2.09, p=0.005). The A allele (PA+PP) of Pro12Ala was significantly associated with the decrease in the risk of EH (OR=0.70, 95%CI: 0.52-0.95, p=0.020). However, C1431T was not significantly associated with EH. Generalized multifactor dimensionality reduction analysis showed that there was a potential gene-gene interaction between C681G and Prol2Ala (p=0.0107). The G-P haplotype (established by C681G, Prol2Ala) was significantly associated with increase in the risk of EH (OR=1.53, 95%CI:1.13-2.07, p=0.006). In conclusion, PPARγ polymorphisms and haplotypes were significantly associated with hypertension susceptibility.