Glutathione peroxidase 1 genotype is associated with an increased risk of coronary artery disease

Coron Artery Dis. 2003 Apr;14(2):149-53. doi: 10.1097/00019501-200304000-00007.

Abstract

Objective: Oxidative stress is implicated in the pathogenesis of many human diseases including atherosclerosis. Human glutathione peroxidase 1 (hgpx1) participates in limiting cellular damage caused by oxidation. A characteristic polyalanine sequence polymorphism in exon 1 of hgpx1 produces three alleles with five, six or seven alanine (ALA) repeats in this sequence. The objective of this study was to determine whether hgpx1 genotype is associated with an altered risk of coronary artery disease (CAD).

Methods: The frequency of the ALA6 allele was determined in 207 men with angiographic evidence of significant CAD compared to a control group (n = 146), by analysing the lengths of polymerase chain reaction fragments containing the ALA repeat polymorphism. Additional information was collected on severity of CAD, presence or absence of a prior acute myocardial infarction (AMI), smoking status, body mass index (BMI) and other clinical data.

Results: There was a significant association between individuals with at least one ALA6 allele and an increased risk of CAD after adjustment for age, BMI and smoking status (odds ratio, 2.07, 95% confidence interval, 1.08-3.99, P = 0.029). However, there was no association between hgpx1 genotype and a previous history of AMI or hgpx1 genotype and severity of CAD.

Conclusion: We conclude that individuals possessing one or two ALA6 alleles appear to be at a modest increased risk of CAD. This observation merits further investigation in other patient populations.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alanine / genetics
  • Alleles
  • Blood Pressure / physiology
  • Body Mass Index
  • Case-Control Studies
  • Coronary Artery Disease / epidemiology*
  • Coronary Artery Disease / genetics*
  • Diastole / physiology
  • Europe / epidemiology
  • Gene Frequency / physiology
  • Genotype
  • Glutathione Peroxidase / genetics*
  • Glutathione Peroxidase GPX1
  • Humans
  • Male
  • Middle Aged
  • Multivariate Analysis
  • Myocardial Infarction / epidemiology
  • Myocardial Infarction / genetics
  • Peptides / genetics
  • Prevalence
  • Risk Factors
  • Risk Reduction Behavior
  • Severity of Illness Index
  • Statistics as Topic
  • Systole / physiology

Substances

  • Peptides
  • polyalanine
  • Glutathione Peroxidase
  • Alanine
  • Glutathione Peroxidase GPX1
  • GPX1 protein, human