Objective: The 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.
Methods: We 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.
Results: The 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).
Conclusions: The epistasis between CYP11B2 and NOS3 and its correlation with varied clinical and biochemical parameters signify its possible contribution in the complex etiology of hypertension.
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