Advances in the genetic basis of coronary artery disease.
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.
Wang
Qing
Q
Department of Molecular Cardiology, Lerner Research Institute/ ND4-38, Cleveland Clinic Foundation, 9500 Euclid Avenue, Cleveland, OH 44195, USA. wangq2@ccf.org
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*
D004268:DNA-Binding Proteins; D026161:MADS Domain Proteins; D064326:MEF2 Transcription Factors; C578035:MEF2A protein, human; D018006:Myogenic Regulatory Factors; D014157:Transcription Factors