B Nikpoor1, G Turecki, C Fournier, P Théroux, G A Rouleau. 1. Center for Research in Neuroscience, McGill University, and the Montreal General Hospital Research Institute, Montreal, Quebec, Canada.
Abstract
BACKGROUND: One of the enzymes involved in the production of free radicals in atherosclerotic plaques is myeloperoxidase (MPO). There is a functional G/A polymorphism 463 bp upstream of the transcription start site of the enzyme with the G allele associated with a higher level of MPO expression than the A allele. Considering the potential role of MPO in the process of atherosclerosis, studying the relationship between this polymorphism and the incidence of coronary artery disease (CAD) seems reasonable. METHOD: We performed a case-control study. The case group consisted of 229 patients who had angiographically proved atherosclerotic plaques in their coronary arteries. The control group consisted of 217 individuals who did not have a history of coronary artery disease, stroke, or peripheral vascular disease. RESULTS: We found that allele A of the MPO gene was less frequent in cases with CAD. In a recessive model patients with the AA genotype had a decreased risk of CAD (odds ratio 0.138, 95% confidence interval 0.040-0.474). In a dominant model a significant protective role for AA or AG versus GG was also detected (odds ratio 0.639, 95% confidence interval 0.436-0.937). CONCLUSION: Our findings suggest that the -463 G/A polymorphism of the MPO gene influences the risk of CAD. This effect may be mediated by the effect of this polymorphism on the transcription level of the MPO gene.
BACKGROUND: One of the enzymes involved in the production of free radicals in atherosclerotic plaques is myeloperoxidase (MPO). There is a functional G/A polymorphism 463 bp upstream of the transcription start site of the enzyme with the G allele associated with a higher level of MPO expression than the A allele. Considering the potential role of MPO in the process of atherosclerosis, studying the relationship between this polymorphism and the incidence of coronary artery disease (CAD) seems reasonable. METHOD: We performed a case-control study. The case group consisted of 229 patients who had angiographically proved atherosclerotic plaques in their coronary arteries. The control group consisted of 217 individuals who did not have a history of coronary artery disease, stroke, or peripheral vascular disease. RESULTS: We found that allele A of the MPO gene was less frequent in cases with CAD. In a recessive model patients with the AA genotype had a decreased risk of CAD (odds ratio 0.138, 95% confidence interval 0.040-0.474). In a dominant model a significant protective role for AA or AG versus GG was also detected (odds ratio 0.639, 95% confidence interval 0.436-0.937). CONCLUSION: Our findings suggest that the -463 G/A polymorphism of the MPO gene influences the risk of CAD. This effect may be mediated by the effect of this polymorphism on the transcription level of the MPO gene.
Authors: Richard A Maki; Vladimir A Tyurin; Robert C Lyon; Ronald L Hamilton; Steven T DeKosky; Valerian E Kagan; Wanda F Reynolds Journal: J Biol Chem Date: 2008-12-05 Impact factor: 5.157
Authors: Lemin Zheng; Benedicta Nukuna; Marie-Luise Brennan; Mingjiang Sun; Marlene Goormastic; Megan Settle; Dave Schmitt; Xiaoming Fu; Leonor Thomson; Paul L Fox; Harry Ischiropoulos; Jonathan D Smith; Michael Kinter; Stanley L Hazen Journal: J Clin Invest Date: 2004-08 Impact factor: 14.808