title: Genetics of coronary artery disease.
abstract: There is almost no data on the genetics of acute coronary syndromes, so this review discusses primarily the 50 genetic risk variants associated with coronary artery disease that are of genome-wide significance in the discovery population and replicated in an independent population. All of these risk variants are extremely common with more than half occurring in >50% of the general population. They increased only minimally the relative risk for coronary artery disease. The most striking finding is that 35 of the 50 risk variants act independently of known risk factors, indicating there are several pathways yet to be appreciated, contributing to the pathogenesis of coronary atherosclerosis and myocardial infarction. All of the genetic variants seem to act through atherosclerosis, except for the ABO blood groups, which show that A and B are associated with increased risk for myocardial infarction, mediated by a prolonged von Willebrand plasma half life leading to thrombosis. The potential molecular mechanisms of 9p21 are discussed, including cell cycle kinase inhibitors. Discovery of risk variants associated with PCSK9 has led to the development of novel treatment for plasma low-density lipoprotein cholesterol. A monoclonal antibody inhibiting PCSK9 has already undergone phase I and II clinical trials, showing it is a potent inhibitor of low-density lipoprotein cholesterol and is mediated through more rapid removal of low-density lipoprotein cholesterol from the plasma. This therapy complements that of statin therapy, which inhibits the synthesis of cholesterol. The benefits of Mendelian randomization to assess safety and efficacy and their limitations are discussed along with future directions.
authors.affiliation: From the Division of Cardiology, University of Ottawa Heart Institute, Ottawa, Ontario, Canada. rroberts@ottawaheart.ca.
authors.forename: Robert
authors.initials: R
authors.lastname: Roberts
mesh_terms: D054058:Acute Coronary Syndrome / Q000453:epidemiology* / Q000235:genetics*; D003324:Coronary Artery Disease / Q000453:epidemiology* / Q000235:genetics*; D020022:Genetic Predisposition to Disease / Q000453:epidemiology / Q000235:genetics; D023281:Genomics; D006801:Humans; D012307:Risk Factors
keywords: base sequence; coronary artery disease; genomics