Endothelial nitric oxide synthase haplotypes are significantly associated with risk of essential hypertension

Background:Nitric Oxide (NO) a potent vasodilator plays a pivotal role in blood pressure regulation. Evidences suggested that eNOS gene polymorphisms are associated with essential hypertension (EHT). We examined the potential association of 4a/4b, A922G, G894T, T786C eNOS gene polymorphisms with EHT in the southern population of Iran.Methods: 200 Iranian patients with EHT and 200 normotensive subjects were included. After collecting demographic data, polymerase chain reaction was used to determine genotype of 4a/4b polymorphism, and three other polymorphisms were analyzed by restriction fragment length polymorphism- polymerase chain reaction method (PCR-RFLP). Pairwise, ternary, and foursome haplotype analysis conducted to reveal their association with ETH. Association was determined by logistic regression analysis.Results: our results demonstrated statistically significant associations between T786C, G894T, and 4a/4a and the disease (P < 0.001) with an increased risk of hypertension (OR = 2, OR = 3.8, OR = 1.6, respectively), however, A922G variant had no significant association. 786C/922A, 786C/922G, 786C/4a, 786C/894T, 922A/4a, and 922G/4a haplotypes were associated an increased risk of hypertension, while 786T/922A, 786T/922G, 786T/894T, and 922A/4b were reversely associated (P < 0.001). Moreover, Ternary haplotype analysis revealed that 786C/922A/4a, 786C/922A/4b, and 786C/922G/4b haplotypes are significantly associated with hypertension while 786T/922G/4a and 786T/922G/894T haplotypes demonstrate protective effects against hypertension (P < 0.001).Conclusion: The 4b/4a and 786T/C polymorphisms emerged as the determinants modifying the risk of hypertension. The 786T/C, 4b/4a and 894G/T polymorphisms, individually and as haplotypes, associated significantly with risk of hypertension. The susceptible haplotypes were associated with an increased risk of hypertension.

Keywords:

Hypertension , NOS3 , polymorphisms , haplotypes