Endothelial Nitric Oxide Synthase Gene Polymorphisms and the Risk of Hypertension in an Indian Population

Abstract

Genetic variants of eNOS gene play a significant role in the pathogenesis of hypertension. Many environmental factors have, also, been implicated in the aetiology of hypertension. We carried out an age-matched case-control study among adults. Hypertension was defined according to JNC-VII criteria and eNOS gene polymorphisms were determined by PCR and PCR followed by PCR-RFLP. eNOS intron 4 aa genotype (adjusted OR 6.81; 95% CI 2.29–20.25) and eNOS 894TT genotype (adjusted OR 7.84; 95% CI 2.57–23.96) were associated with the risk of hypertension. Tobacco users (either smoking/chewing or both) with eNOS intron 4 aa genotype (OR 14.00: 95% CI 1.20–163.37), eNOS 894GG genotype (OR 5.56: 95% CI 3.72–8.31), and eNOS T-786C CC genotype (OR 9.00: 95% CI 1.14–71.04) were at an increased risk of hypertension. Similarly a significant gene-environment interaction was observed between individuals consuming alcohol with eNOS intron 4 aa genotype (OR 12.00: 95% CI 1.20–143.73) and eNOS 894GG genotype (OR 1.95: 95% CI 1.35–2.81). The present study identified few susceptible genotypes of the eNOS gene with the risk of hypertension. Moreover, the interactive effects between the environmental factors and the risk of hypertension were dependent on the eNOS genotypes.

A multilevel prediction of physiological response to challenge: Interactions among child maltreatment, neighborhood crime, endothelial nitric oxide synthase gene (eNOS), and GABA(A) receptor subunit alpha-6 gene (GABRA6)

“…For example, polymorphisms of the eNOS G894T gene have been linked to difficulties regulating heart rate and blood pressure. The presence of the T allele of this gene has been implicated in pathological conditions, including greater risk for hypertension (Shankarishan, Borah, Ahmed, & Mahanta, 2014). Conversely, homozygosity of the G allele is associated with lower diastolic blood pressure during a physical challenge (Nunes, Barroso, Pereira, Krieger, & Mansur, 2014).…”

“…Conversely, homozygosity of the G allele is associated with lower diastolic blood pressure during a physical challenge (Nunes, Barroso, Pereira, Krieger, & Mansur, 2014). It appears that the presence of the T allele alters the structure of eNOS and affects its activity by decreasing production of nitric oxide, which ultimately leads to higher blood pressure (Shankarishan et al, 2014).…”

“…A somewhat surprising finding in at least one study was a significant gene–environment interaction between eNOS and behavioral risk factors like chewing tobacco and consuming alcohol. Specifically, the GG genotype was associated with increased risk for hypertension among individuals who used tobacco or consumed alcohol (Shankarishan et al, 2014). The molecular effect of the GG polymorphism on eNOS enzyme function in this case is still not clear, although several mechanisms have been proposed including stimulation of the sympathetic nervous system and inhibition of nitric oxide (Randin, 1995; Yamada, 2004).…”

Features of clinical and laboratory indicators in alcoholic liver disease in combination with arterial hypertension depending on T786C polymorphism of the eNOS gene

“…Зниження базаль-ної продукції NO може призводити до розвитку АГ, тромбозу та вазоспазму. Багатьма дослідженнями в різних популяціях показана асоціація розвитку АГ із поліморфізмом гена eNOS, зокрема із T786C [8,9,10,11]. З іншого боку, доведена потенційна роль NO в абдомінальній гемодинаміці при захворюваннях печінки.…”

Comparison of bleeding time changes in essential hypertension patients on losartan or amlodipine: a prospective observational study

“…It has been found that Inhibition of eNOS elevates blood pressure in healthy humans and in mice disruption of eNOS gene leads to hypertension. 5 In hypertension, shear due to increased pressure can cause endothelial damage as the mechanisms of normal vascular remodeling is faulty due to impaired structural adaptation to elevated blood pressure and vasoconstriction. 6,7 When the vessel wall is damaged, sub endothelial matrix is exposed and platelets adhere to collagen with the help of α2β1 and glycoprotein(GP)V1 and to Von Williebrand factor (vWF) with the help of GPIbα and GPIIb/IIIa present on the platelet surface.…”