Genetic markers of oxidative stress and coronary atherosclerosis.
Atherosclerosis, the primary cause of coronary artery disease (CAD), is a multifactorial disease, the molecular etiology of which involves interaction of many genes and environmental factors. Reactive oxygen species are integral to many cellular and biomolecular processes that are active in the transition of incipient fatty streaks into acute coronary syndromes. Animal models of atherosclerosis and correlative data from human studies support the oxidative stress hypothesis of atherosclerosis. However, the association of genetic polymorphisms that underlie enhanced oxidative stress with CAD is controversial. In this review, we discuss polymorphisms in genes that are main sources of reactive oxygen species generation (NADH oxidase, endothelial nitric oxide synthase, and myeloperoxidase) in mitochondria and the antioxidant enzymes paraoxonase, glutathione reductase, and heme oxygenase. The contribution of defined genetic variants involved in oxidative homeostasis to human atherosclerosis susceptibility is modest because regulation of oxidative stress is multifactorial. However, the contribution of genetic haplotypes in concert with environmental factors is likely significant. A more rigorous characterization of genetic and oxidative phenotypes together with characterization of novel gene polymorphisms may help in early therapeutic intervention for CAD.
Madamanchi
Nageswara R
NR
Department of Medicine, University of North Carolina, 3033 Old Clinic Building, Chapel Hill, NC 27599, USA.
Tchivilev
Igor
I
Runge
Marschall
M
D000818:Animals; D003324:Coronary Artery Disease / Q000235:genetics*; D005819:Genetic Markers; D020022:Genetic Predisposition to Disease; D006419:Heme Oxygenase (Decyclizing) / Q000378:metabolism; D006801:Humans; D008928:Mitochondria / Q000378:metabolism; D008954:Models, Biological; D019001:Nitric Oxide Synthase / Q000378:metabolism; D018384:Oxidative Stress; D011110:Polymorphism, Genetic; D017382:Reactive Oxygen Species
D005819:Genetic Markers; D017382:Reactive Oxygen Species; D019001:Nitric Oxide Synthase; D006419:Heme Oxygenase (Decyclizing)