背景:最近的研究报道NOS3在心血管病理学中起重要作用,而NOS3和高血压(HT)的关联在非洲裔美国人和欧洲白人之间一直存在争议。这里,我们旨在进一步研究未探索的NOS3基因座对汉族人群HT易感性的遗传影响。
结果:在一项病例对照研究中测试了三种多态性rs4496877,rs1808593和rs3918186与HT的关联,该研究包括2012例HT病例和2210例对照。关联分析表明,在整个研究人群中,NOS3的rs4496877,rs1808593和rs3918186与HT之间没有显着关联。分层分析表明,≥55岁人群rs3918186与HT显著相关(OR=1.245,95%CI=1.010~1.534,P=0.04)。rs4496877和rs1808593在男性人群(P=0.015)和<55岁人群(P=0.025)中与HT显著相关,分别为(OR=3.254,95%CI=1.257-8.425,OR=1.683,95%CI=1.066-2.657)。数量性状分析表明,各基因型(AA,非干预人群中rs3918186的AT和TT)(P=0.016)。GMDR分析表明,饮酒和rs3918186对HT的风险具有显着的交互作用。
结论:这项研究的结果表明,NOS3的rs4496877,rs1808593和rs3918186多态性与HT的遗传易感性有关,rs3918186与中国人群的SBP有关。年龄和性别可能会改变NOS3对HT的遗传效应,饮酒与rs3918186有显著的相互作用。
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.
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.