Genetic polymorphisms and endothelial dysfunction in patients with essential hypertension: a cross-sectional case-control study.

BACKGROUND: Both in animal models and humans an association between endothelial constitutive nitric oxide synthase (ecNOS) gene polymorphism and the development of hypertension has been found. However, the relation between ecNOS polymorphism and endothelial function in patients with hypertension has not been systematically studied. Genes of the renin-angiotensin system include the angiotensin-converting enzyme (ACE) gene, and the angiotensin II type 1 receptor (ATIR) gene, and have been associated with essential hypertension. However, no consistent data are available about the relation between polymorphisms of these genes and the presence of endothelial dysfunction in such patients.
OBJECTIVES: To assess the presence of genetic polymorphisms and of endothelial dysfunction in patients with essential hypertension. To determine the effects of gene polymorphisms on endothelial dysfunction in these subjects.
METHODS: In 129 patients with essential hypertension and the same number of age-matched controls polymorphisms of the ecNOS gene, ACE gene, and AT1R gene were analysed by polymerase chain reactions. Endothelial function was assessed by maximal endothelial dependent vasodilation in response to reactive hyperaemia using high resolution ultrasound examinations of the brachial arteries. To assess correlation between genetic markers, endothelial function, and the presence of hypertension both univariate and multivariate analyses were used including Pearson's and Spearman's correlation coefficients, and multiple logistic regressions.
RESULTS: The size of endothelium-dependent vasodilation between patients and controls differed by 16% (p<0.02). However, the presence of genetic polymorphisms of the ecNOS, ACE, and AT1R genes did not significantly differ between patients and controls. Neither were there any statistically significant differences in endothelial function between various genotypes of the three genes. This was so for both the patients and the controls, although in all of these comparisons the controls overall displayed a slightly better endothelial function than the patients did. Multiple regression analysis with endothelial dysfunction as dependent and the presence of gene polymorphisms as independent variables did not reveal any significant correlation either.
CONCLUSION: A significant relation between endothelial dysfunction and essential hypertension was demonstrated. However, no relations between genetic markers and the presence of essential hypertension or between endothelial dysfunction and genetic markers were established. The failure of our study to demonstrate the latter may be due to confounders. Also, other genes may be more important in the pathogenesis of endothelial dysfunction and essential hypertension. The current study underscores that endothelial dysfunction and hypertension are not simple genetic disorders, and that they are, essentially, multicausal.