Association study of NOS3 gene polymorphisms and hypertension in the Han Chinese population

Background: Recent studies have reported that NOS3 plays an important role in cardiovascular pathology, whereas the association of NOS3 and hypertension (HT) has been controversial between African Americans and European whites. Here, we aimed to further investigate the genetic effect of unexplored loci at NOS3 on the susceptibility of HT in the Han Chinese population.

Methods and results: The association of three polymorphisms; rs4496877, rs1808593 and rs3918186 to HT was tested in a case control study that included 2012 HT cases and 2210 controls. Association analysis showed that there was no significant association between rs4496877, rs1808593 and rs3918186 of NOS3 and HT in the whole study population. Stratification analysis indicated that rs3918186 was significantly associated with HT in the ≥55-year-old population (OR = 1.245, 95% CI = 1.010-1.534, P = 0.04). The rs4496877 and rs1808593 were significantly associated with HT in the male population (P = 0.015) and <55-year-old population (P = 0.025), respectively (OR = 3.254, 95% CI = 1.257-8.425 and OR = 1.683, 95% CI = 1.066-2.657, respectively). Quantitative trait analysis showed that there were significant differences in systolic blood pressure (SBP) among the genotypes (AA, AT and TT) of rs3918186 in the non-intervention populations (P = 0.016). GMDR analysis showed that drinking and rs3918186 had significant interaction effects for risk of HT.

Conclusions: The findings of this study indicated that the rs4496877, rs1808593 and rs3918186 polymorphisms of NOS3 contribute to the genetic susceptibility of HT and that rs3918186 was associated with SBP in the Chinese population. Age and gender might modify the genetic effect of NOS3 on HT, and drinking significantly interacts with rs3918186.