title: Advances in the genetic basis of coronary artery disease.
abstract: Exciting advances have been made recently in genetic studies of coronary artery disease (CAD), myocardial infarction (MI), and ischemic stroke. One disease-causing gene for CAD and MI has been identified as MEF2A, which is located on chromosome 15q26.3 and encodes a transcriptional factor with a high level of expression in coronary endothelium. Approximately 1% to 2% of CAD patients may carry an MEF2A mutation. Four new susceptibility genes have been identified using genome-wide association studies or genome-wide linkage studies: LTA (encoding cytokine lymphotoxin-alpha) on 6p21.3 for MI; LGALS2 (encoding galectin-2, an LTA-interacting protein) on 22q12-q13 for MI; ALOX5AP (encoding 5-lipoxygenase activating protein involved in synthesizing potent pro-inflammatory leukotrienes) on 13q12-13 for MI and stroke; and PDE4D (encoding phosphodiesterase 4D) on 5q12 for ischemic stroke. These studies identify a new mechanism, the myocyte enhancer factor 2 (MEF2) signaling pathway of vascular endothelium, for the pathogenesis of CAD, and also confirm the role of inflammation in the disease process.
authors.affiliation: Department of Molecular Cardiology, Lerner Research Institute/ ND4-38, Cleveland Clinic Foundation, 9500 Euclid Avenue, Cleveland, OH 44195, USA. wangq2@ccf.org
authors.forename: Qing
authors.initials: Q
authors.lastname: Wang
mesh_terms: D000818:Animals; D002884:Chromosomes, Human, Pair 15 / Q000235:genetics*; D003324:Coronary Artery Disease / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D003331:Coronary Vessels / Q000378:metabolism / Q000473:pathology; D004268:DNA-Binding Proteins / Q000235:genetics*; D004730:Endothelium, Vascular / Q000378:metabolism / Q000473:pathology; D008040:Genetic Linkage; D020022:Genetic Predisposition to Disease; D006801:Humans; D026161:MADS Domain Proteins; D064326:MEF2 Transcription Factors; D009154:Mutation; D018006:Myogenic Regulatory Factors; D014157:Transcription Factors / Q000235:genetics*; D014158:Transcription, Genetic / Q000235:genetics*
chemical_list: D004268:DNA-Binding Proteins; D026161:MADS Domain Proteins; D064326:MEF2 Transcription Factors; C578035:MEF2A protein, human; D018006:Myogenic Regulatory Factors; D014157:Transcription Factors