Peroxisome proliferator-activated receptor-gamma2-Pro12Ala and endothelial nitric oxide synthase-4a/b gene polymorphisms are associated with essential hypertension

Abstract

Objective Peroxisome proliferator-activated receptor-gamma2 (PPARgamma2) belongs to the family of the nuclear hormone receptors and has been recently implicated in vascular biology. PPARgamma2(Pro12Ala) gene polymorphism is associated with obesity, body mass index and diabetes mellitus. The endothelial nitric oxide synthase (eNOS) (4a/b) gene polymorphism contributes to coronary heart disease and hypertension risk. We tested whether both polymorphic variants were associated with hypertension risk, and their inter-relationship with plasma homocysteine.Design A case-control study was conducted selecting 235 subjects with arterial hypertension and 223 normotensive matched controls.Methods Genotyping for the PPARgamma2(Pro12Ala) and the eNOS(4a/b) were performed by mutagenically separated polymerase chain reaction and by polymerase chain reaction. Glucose, lipid profile, plasma creatinine, homocysteine and microalbuminuria were measured.Results We found a significant contribution of the PPARgamma2(Pro12Ala) and eNOS(4a/b) gene polymorphisms to hypertensive risk in our population (odds ratio, 1.9 and 1.6, respectively), confirmed by multiple logistic regression analysis. Those subjects with normal plasma homocysteine values had an increased hypertensive risk with an odds ratio of 2.6 for the PP genotype of the PPARgamma2 gene and an odds ratio of 1.8 for the a allele of the eNOS gene.Conclusions Both analyzed polymorphisms were associated in a synergistic manner with hypertension. This effect manifested only in those subjects with normal homocysteine plasma values. Our findings suggest complex genotype-environmental interactions on hypertensive risk.