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.

Atherosclerosis
|January 12, 2007
PubMed

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.

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