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Published on: October 12, 2017
NAD(P)H oxidase polymorphism (C242T) and high HDL cholesterol associate with recurrent coronary events in
James P Corsetti1, Dan Ryan1, Arthur J Moss2
1Department of Pathology and Laboratory Medicine, University of Rochester School of Medicine and Dentistry, Rochester, NY, USA.
Insights
High C-reactive protein (CRP) and high cholesterol identify high-risk heart attack patients. Oxidative stress, linked to a specific gene variant, significantly increases recurrent coronary event risk in this group.
Area of Science:
- Cardiology
- Genetics
- Biochemistry
Background:
- A subgroup of postinfarction patients with inflammation (high C-reactive protein) and hypercholesterolemia face elevated risk for recurrent coronary events.
- Within this high-risk group, elevated high-density lipoprotein cholesterol (HDL-C) was identified as an additional risk factor among metabolic, inflammatory, and thrombogenic markers.
Purpose of the Study:
- To investigate the role of oxidative stress in this high-risk subgroup of postinfarction patients.
- To examine the impact of a specific polymorphism in the NAD(P)H oxidase enzyme (p22phox C242T) on recurrent coronary event risk.
Main Methods:
- The study analyzed 663 non-diabetic patients from the THROMBO postinfarction study with complete blood marker and genotyping data.
- Cox multivariable regression, adjusted for clinical covariates, was employed to assess risk associated with blood markers and the p22phox C242T polymorphism.
- The T allele of the C242T polymorphism was associated with decreased NAD(P)H oxidase activity.
Main Results:
- Elevated HDL-C was significantly associated with increased risk (Hazard Ratio [HR] 2.62, 95% Confidence Interval [CI] 1.05-6.55, p=0.039).
- The C242T polymorphism (CC genotype vs. CT plus TT genotypes) showed significant independent risk (HR 3.14, 95% CI 1.34-7.35, p=0.0084).
Conclusions:
- Oxidative stress, influenced by the p22phox C242T polymorphism, plays a significant role in the risk of recurrent coronary events.
- These findings highlight the importance of considering oxidative stress in managing high-risk postinfarction patients defined by inflammation and hypercholesterolemia.
Abstract:
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.
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