Christchurch Cardioendocrine Research Group, Department of Medicine, University of Otago-Christchurch, Christchurch, New Zealand.
J Mol Cell Cardiol. 2011 Apr;50(4):695-701. doi: 10.1016/j.yjmcc.2011.01.010. Epub 2011 Jan 27.
Polymorphisms within individual natriuretic peptide genes have been associated with risk factors for cardiovascular disease, but their association with clinical outcomes was previously unknown. This study aimed to investigate the association between genetic variants in key genes of the natriuretic peptide system with cardiovascular outcomes in patients with coronary artery disease. Coronary disease patients (n=1810) were genotyped for polymorphisms within NPPA, NPPB, NPPC, NPR1 and NPR2. Clinical history, natriuretic peptide concentrations, echocardiography, all-cause mortality and cardiovascular hospital readmissions were recorded over a median 2.8 years. Minor alleles of NPPA rs5068, rs5065 and rs198358 were associated with less history of hypertension; minor alleles of NPPA rs5068 and rs198358 was also associated with higher circulating natriuretic peptide levels (p=0.003 to p=0.04). Minor alleles of NPPB rs198388, rs198389, and rs632793 were associated with higher circulating BNP and NT-proBNP (p=0.001 to p=0.03), and reduced E/E(1) (p=0.011), or LVESVI (p=0.001) and LVEDVI (p=0.004). Within NPPC, both rs11079028 and rs479651 were associated with higher NT-proBNP and CNP (p=0.01 to p=0.03), and rs479651 was associated with lower LVESVI (p=0.008) and LVEDVI (p=0.018). NPR2 rs10758325 was associated with smaller LVMI (p<0.02). A reduced rate of cardiovascular readmission was observed for minor alleles of NPPA rs5065 (p<0.0001), NPPB rs632793 (p<0.0001), rs198388 (p<0.0001), rs198389 (p<0.0001), and NPR2 rs10758325 (p<0.0001). There were no associations with all-cause mortality. In established cardiovascular disease, natriuretic peptide system polymorphisms were associated with natriuretic peptide levels, hypertension, echocardiographic indices and the incidence of hospital readmission for cardiovascular events.
个体利钠肽基因内的多态性与心血管疾病的危险因素有关，但它们与临床结果的关联以前是未知的。本研究旨在探讨心脏疾病患者中利钠肽系统关键基因内遗传变异与心血管结局之间的关系。对 1810 名冠心病患者进行了 NPPA、NPPB、NPPC、NPR1 和 NPR2 基因内多态性的基因分型。中位随访 2.8 年期间，记录了临床病史、利钠肽浓度、超声心动图、全因死亡率和心血管住院再入院情况。NPPA rs5068、rs5065 和 rs198358 的次要等位基因与高血压病史较少有关；NPPA rs5068 和 rs198358 的次要等位基因也与循环利钠肽水平较高有关（p=0.003 至 p=0.04）。NPPB rs198388、rs198389 和 rs632793 的次要等位基因与循环 BNP 和 NT-proBNP 水平较高有关（p=0.001 至 p=0.03），E/E(1) 比值较低（p=0.011），LVESVI 较低（p=0.001）和 LVEDVI 较低（p=0.004）。在 NPPC 中，rs11079028 和 rs479651 均与 NT-proBNP 和 CNP 水平较高有关（p=0.01 至 p=0.03），rs479651 与 LVESVI 较低（p=0.008）和 LVEDVI 较低（p=0.018）有关。NPR2 rs10758325 与较小的 LVMI 有关（p<0.02）。NPPA rs5065（p<0.0001）、NPPB rs632793（p<0.0001）、rs198388（p<0.0001）、rs198389（p<0.0001）和 NPR2 rs10758325（p<0.0001）的次要等位基因观察到心血管再入院率降低。与全因死亡率无关联。在已确诊的心血管疾病中，利钠肽系统多态性与利钠肽水平、高血压、超声心动图指标以及心血管事件住院再入院的发生率有关。
