Molecular genetics of coronary artery disease

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.

Figure 1. Evolution of our views of the pathophysiology of atherosclerosis (coronary artery disease and myocardial infarction)

Views of the pathophysiology of coronary artery disease have evolved over time.