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


CONCLUSIONS
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.
Winter
Julian P
JP
Academic Unit of Epidemiology and Health Services Research, University of Leeds, UK.
Gong
YunYun
Y
Grant
Peter J
PJ
Wild
Christopher P
CP
D000409:Alanine / Q000235:genetics; D000483:Alleles; D001794:Blood Pressure / Q000502:physiology; D015992:Body Mass Index; D016022:Case-Control Studies; D003324:Coronary Artery Disease / Q000453:epidemiology* / Q000235:genetics*; D003971:Diastole / Q000502:physiology; D005060:Europe / Q000453:epidemiology; D005787:Gene Frequency / Q000502:physiology; D005838:Genotype; D005979:Glutathione Peroxidase / Q000235:genetics*; D006801:Humans; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D009203:Myocardial Infarction / Q000453:epidemiology / Q000235:genetics; D010455:Peptides / Q000235:genetics; D015995:Prevalence; D012307:Risk Factors; D040242:Risk Reduction Behavior; D012720:Severity of Illness Index; D013223:Statistics as Topic; D013599:Systole / Q000502:physiology; D000094765:Glutathione Peroxidase GPX1
D010455:Peptides; C019529:polyalanine; D005979:Glutathione Peroxidase; D000409:Alanine; D000094765:Glutathione Peroxidase GPX1; C000722067:GPX1 protein, human