Molecular genetics of coronary artery disease.
OBJECTIVE
Coronary artery disease, including its most severe complication myocardial infarction, is the leading cause of death; however, its genetic studies lag behind other diseases. Many advances have recently been made, however, and these are reviewed here.


RESULTS
Positional cloning based on genome-wide linkage analysis with large families identified the first non - lipid-related disease-causing gene, MEF2A (encoding a transcriptional factor), for coronary artery disease and myocardiaI infarction. The MEF2A mutations may account for up to 1.93% of the disease population; thus, genetic testing based on mutational analysis of MEF2A may soon be available for many coronary artery disease/myocardial infarction patients. Genome-wide association studies identified significant association for myocardiaI infarction with the LTA gene (encoding lymphotoxin-alpha), and a follow-up study found that an LTA-interacting gene, LGALS2 (encoding galectin-2), is also a susceptibility gene for myocardiaI infarction. Studies that employ genome-wide linkage scans with hundreds of small nuclear families have identified new susceptibility genes for coronary artery disease and myocardiaI infarction, including ALOX5AP (encoding 5-lipoxygenase-activating protein) associated with myocardial infarction and stroke and PDE4D (encoding phosphodiesterase 4D) for ischemic stroke.


CONCLUSIONS
Genetic studies provide new insights into the pathogenesis of coronary artery disease and myocardial infarction. Future studies will focus on identification of new disease-causing genes and susceptibility genes, exploration of the molecular mechanisms by which mutations cause coronary artery disease/myocardiaI infarction, and gene-specific therapies for patients.
Wang
Qing
Q
Department of Molecular Cardiology, Lerner Research Institute, The Cleveland Clinic Foundation, Cleveland, OH 44195, USA. wangq2@ccf.org
D015105:3',5'-Cyclic-AMP Phosphodiesterases / Q000235:genetics; D058927:5-Lipoxygenase-Activating Proteins; D002352:Carrier Proteins / Q000235:genetics; D003327:Coronary Disease / Q000235:genetics* / Q000378:metabolism; D054684:Cyclic Nucleotide Phosphodiesterases, Type 3; D054703:Cyclic Nucleotide Phosphodiesterases, Type 4; D004268:DNA-Binding Proteins / Q000235:genetics; D008040:Genetic Linkage; D020022:Genetic Predisposition to Disease; D006801:Humans; D008233:Lymphotoxin-alpha / Q000235:genetics; D026161:MADS Domain Proteins; D064326:MEF2 Transcription Factors; D008565:Membrane Proteins / Q000235:genetics; D008967:Molecular Biology; D009154:Mutation; D018006:Myogenic Regulatory Factors; D014157:Transcription Factors / Q000235:genetics
D058927:5-Lipoxygenase-Activating Proteins; C548592:ALOX5AP protein, human; D002352:Carrier Proteins; D004268:DNA-Binding Proteins; D008233:Lymphotoxin-alpha; D026161:MADS Domain Proteins; D064326:MEF2 Transcription Factors; C578035:MEF2A protein, human; D008565:Membrane Proteins; D018006:Myogenic Regulatory Factors; D014157:Transcription Factors; D015105:3',5'-Cyclic-AMP Phosphodiesterases; D054684:Cyclic Nucleotide Phosphodiesterases, Type 3; D054703:Cyclic Nucleotide Phosphodiesterases, Type 4; C517376:PDE4D protein, human