NAD(P)H oxidase polymorphism (C242T) and high HDL cholesterol associate with recurrent coronary events in postinfarction patients

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• 作者：James P. Corsetti ; Dan Ryan ; Arthur J. Moss ; Wojciech Zareba ; Charles E. Sparks
• 关键词：HDL ; Vascular NAD(P)H oxidase ; p22phox ; C242T polymorphism ; Recurrent coronary risk ; Oxidative stress
• 刊名：Atherosclerosis
• 出版年：2008
• 出版时间：January 2008
• 年：2008
• 卷：196
• 期：1
• 页码：461-468
• 全文大小：609 K

文摘

We recently identified a subgroup of postinfarction patients at high-risk for recurrent coronary events defined by inflammation (high C-reactive protein) (CRP) and hypercholesterolemia. Within this subgroup, only elevated high-density lipoprotein cholesterol (HDL-C) from a set of metabolic, inflammatory and thrombogenic blood markers was associated with additional risk. To investigate the role of oxidative stress in this high-risk subgroup, we examined effects on risk of a polymorphism known to affect functional activity of NAD(P)H oxidase, an oxidative enzyme associated with generation of reactive oxygen species. The study population comprised non-diabetic patients of thrombogenic factors and recurrent coronary events (THROMBO) postinfarction study having complete blood marker and genotyping results (N = 663) for C242T polymorphism of p22phox subunit (T allele associated with decreased activity). Cox multivariable regression, adjusted for significant clinical covariates, was used to assess within-subgroup risk associated with blood markers and polymorphism. In addition to elevated HDL-C (hazard ratio, 95 % CI and p-value; 2.62, 1.05–6.55 and 0.039), significant independent risk was found for C242T (CC versus CT plus TT: 3.14, 1.34–7.35 and 0.0084). We conclude that oxidative stress plays a significant role in establishment of risk for recurrent coronary events in a high-risk subgroup of postinfarction patients defined by inflammation and hypercholesterolemia.