Advances in the genetic basis of coronary artery disease

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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-α) 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 proinflammatory 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.