Endothelial nitric oxide synthase gene polymorphisms are associated with cardiovascular risks in prehypertensives

Abstract

Though endothelial nitric oxide synthase (eNOS) gene polymorphism is documented in the causation of hypertension, its role in prehypertension has not been investigated. The present study was conducted in 172 subjects divided into prehypertensives (n = 57) and normotensives (n = 115). Cardiovascular (CV) parameters including baroreflex sensitivity (BRS) by continuous BP variability assessment and sympathovagal imbalance (SVI) by heart rate variability analysis were recorded. Biochemical parameters for insulin resistance (homeostatic model for assessment of insulin resistance), oxidative stress, lipid risk factors, renin, and inflammatory parameters were measured. Genotyping for eNOS polymorphisms rs1799983 (298G>T) and rs2070744 (-786T>C) was performed by polymerase chain reaction-restriction fragment length polymorphism method. Multiple regression analysis was done to assess the association between SVI and metabolic markers, and multivariate logistic regression was done to determine the prediction of prehypertension status by genotype, BRS, and ratio of low-frequency to high-frequency in these subjects. The BP variability, heart rate variability, and biochemical parameters were significantly altered in prehypertensives. The eNOS polymorphisms were found to be associated with prehypertension. BRS, the marker of SVI, was significantly associated with BP, homeostatic model for assessment of insulin resistance, and tumor necrosis factor alpha in 298GG genotype of prehypertensive population. The eNOS gene polymorphisms appear to be associated with prehypertension. 298G>T and -786T>C contribute to SVI in young prehypertensives attributed by insulin resistance and inflammation. The CV risks were associated with prehypertension status in prehypertensives expressing both 298GG and -786TT genotypes. Association of CV risks with SVI appears to be stronger in prehypertensives expressing GG genotype.