984G>T/Glu298Asp Endothelial nitric oxide synthase gene polymorphism and its association with the biodisponibility of nitric oxide and hypertension in Venezuela

Objective: Detection of the 984G>T endothelial nitric oxide synthase (eNOS) genotype and the association with essential hypertension and Nitric Oxide (NO) serum level in the Venezuelan population. Methods: Samples from 192 patients with hypertension and 192 control subjects were analyzed for genotyping 984G>T eNOS polymorphism. A subset of 78 samples underwent the determination of serum NO concentration (μM). Results: The frequency for the GT genotype was 31.77 % in hypertensive individuals vs 33.85 % in controls individuals; and 6.25 % and 1.56 % respectively, for TT genotype; corresponding to T allelic frequency of 0.23 in hypertensive individuals. The OR for hypertensive individuals carriers for the T allele was 1.12 (IC 95%: 0.72-1.72, p>0.05). In contrast, the Odds ratio (OR), considering only the GG vs TT genotypes, we found a statistically significant 4.17 fold increased risk for hypertension (OR= 4.17, 95% CI: 1.06-19.11, p<0.05). Additionally, we found a significant decrease in serum concentrations of nitric oxide (46.47%; p<0.05) in the subgroup of carriers of the risk allele T (13.80±4.85 μM, n=35), compared with the subgroup GG (25.78±16.75 μM, n=43). Conclusions: These results suggest that the T risk allele of the polymorphism 984G>T in the eNOS gene, the main enzyme responsible for NO synthesis in endothelial level, may be associated with decreased serum levels of NO as intermediate phenotype, and this in turn be associated with the development of hypertension and clinical phenotype