The epistasis between vascular homeostasis genes is apparent in essential hypertension

ObjectiveThe epistasis influence of vascular homeostasis genes is vital to multigenetic diseases. This study was designed to perceive the possible role of epistasis in the etiology of essential hypertension.MethodsWe investigated seven polymorphisms of ACE, CYP11B2 and NOS3 epistatically, and SBP, DBP, MAP, ACE activity, plasma aldosterone concentration (PAC) and NOx level in 860 age- and ethnicity-matched unrelated north-Indian subjects.ResultsThe hypertension risk in individuals with interacted-genotypes (IwIw + IwIc) + (4aa), (IcIc) + (4bb + 4ba) and IcIc + 4aa of the CYP11B2 and NOS3 was significantly higher with odds ratio 5.5 (95% CI = 2.9–10.6, P < 0.0001), 2.4 (95% CI = 1.4–4.1, P < 0.0008) and 7.5 (95% CI = 1.6–34.8, P = 0.010), respectively. The odds ratio for hypertension with interacted-haplotypes (−344T/Ic) + (−922A/−786T/4a/894G) and (−344T/Ic) + (−922G/−786C/4a/894G) of CYP11B2 and NOS3 was 5.3 (95% CI = 2.0–14.2, P = 0.005) and 3.9 (95% CI = 1.4–10.4, P = 0.04), respectively; whereas for the protective interacted-haplotypes (−344T/Iw) + (−922A/−786T/4b/894G), the odds ratio was 0.7 (95% CI = 0.5–0.9, P = 0.03). While the interacted-genotypes, IcIc + 4aa correlated with higher SBP and MAP (P = 0.006; P = 0.04), the interacted-haplotypes, (−344T/Ic) + (−922A/−786T/4a/894G) and (−344T/Ic) + (−922G/−786C/4a/894G) correlated with higher MAP and lower NOx level (P = 0.02 and P = 0.03, respectively), and the protective interacted-haplotypes (−344T/Iw) + (−922A/−786T/4b/894G) correlated with lower PAC and MAP (P = 0.024 and P = 0.018, respectively).ConclusionsThe epistasis between CYP11B2 and NOS3 and its correlation with varied clinical and biochemical parameters signify its possible contribution in the complex etiology of hypertension.