Molecular genetics of coronary artery disease

Curr Opin Cardiol. 2005 May;20(3):182-8. doi: 10.1097/01.hco.0000160373.77190.f1.

Abstract

Purpose of review: 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.

Recent findings: 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.

Summary: 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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.
  • Review

MeSH terms

  • 3',5'-Cyclic-AMP Phosphodiesterases / genetics
  • 5-Lipoxygenase-Activating Proteins
  • Carrier Proteins / genetics
  • Coronary Disease / genetics*
  • Coronary Disease / metabolism
  • Cyclic Nucleotide Phosphodiesterases, Type 3
  • Cyclic Nucleotide Phosphodiesterases, Type 4
  • DNA-Binding Proteins / genetics
  • Genetic Linkage
  • Genetic Predisposition to Disease
  • Humans
  • Lymphotoxin-alpha / genetics
  • MADS Domain Proteins
  • MEF2 Transcription Factors
  • Membrane Proteins / genetics
  • Molecular Biology*
  • Mutation
  • Myogenic Regulatory Factors
  • Transcription Factors / genetics

Substances

  • 5-Lipoxygenase-Activating Proteins
  • ALOX5AP protein, human
  • Carrier Proteins
  • DNA-Binding Proteins
  • Lymphotoxin-alpha
  • MADS Domain Proteins
  • MEF2 Transcription Factors
  • MEF2A protein, human
  • Membrane Proteins
  • Myogenic Regulatory Factors
  • Transcription Factors
  • 3',5'-Cyclic-AMP Phosphodiesterases
  • Cyclic Nucleotide Phosphodiesterases, Type 3
  • Cyclic Nucleotide Phosphodiesterases, Type 4
  • PDE4D protein, human