Multi-locus interactions of vascular homeostasis genes in essential hypertension: A gender-based study

BackgroundStudies on genes of endothelial and vascular homeostasis are inadequate in females.MethodsWe investigated the role of 7 variants of ACE, AGT and NOS3 and their correlation with NOx levels and ACE activity in hypertension susceptibility in 910 case–controls of both genders.ResultsPrevalence of alleles D of ACE I/D; − 6A of AGT − 6G/A; − 786C, 894T and 4a of NOS3 − 786T/C, 894G/T and 4b/4a polymorphisms was observed in patients (P ≤ 0.05). The 3 genotypes-combinations containing 6 + 5 wild-type alleles of AGT and NOS3 were significantly less prevalent in patients (P ≤ 0.0003). The haplotypes 235T/174T/− 6A of AGT (P = 4E− 3) and − 786T/894G/4a and − 786C/894G/4a of NOS3 (P = 2E− 3, P = 0.011, respectively) were significantly more prevalent in patients. The AGT and NOS3 findings were similar in males. Genotypes-combinations with 6 + 5 wild-type alleles of AGT correlated with higher NOx levels (P = 0.03). The NOS3 genotypes-combinations having 6 and 6 + 5 wild-type alleles correlated with decreased ACE activity (P = 0.025, P = 0.0015, respectively) and increased NOx levels (P = 0.001, P = 0.0001, respectively) in patients. In gene–gene interactions, ACE D allele associated with ≤ 4 wild-type alleles containing genotypes-combinations of AGT and NOS3 in patients (P ≤ 0.04).ConclusionWithin gene and between genes interactions of variants influence ACE activity and NOx levels and associate with EH.