Peer-review started: May 3, 2015
First decision: August 4, 2015
Revised: October 18, 2015
Accepted: November 10, 2015
Article in press: November 11, 2015
Published online: January 26, 2016
Atherosclerotic coronary artery disease (CAD) comprises a broad spectrum of clinical entities that include asymptomatic subclinical atherosclerosis and its clinical complications, such as angina pectoris, myocardial infarction (MI) and sudden cardiac death. CAD continues to be the leading cause of death in industrialized society. The long-recognized familial clustering of CAD suggests that genetics plays a central role in its development, with the heritability of CAD and MI estimated at approximately 50% to 60%. Understanding the genetic architecture of CAD and MI has proven to be difficult and costly due to the heterogeneity of clinical CAD and the underlying multi-decade complex pathophysiological processes that involve both genetic and environmental interactions. This review describes the clinical heterogeneity of CAD and MI to clarify the disease spectrum in genetic studies, provides a brief overview of the historical understanding and estimation of the heritability of CAD and MI, recounts major gene discoveries of potential causal mutations in familial CAD and MI, summarizes CAD and MI-associated genetic variants identified using candidate gene approaches and genome-wide association studies (GWAS), and summarizes the current status of the construction and validations of genetic risk scores for lifetime risk prediction and guidance for preventive strategies. Potential protective genetic factors against the development of CAD and MI are also discussed. Finally, GWAS have identified multiple genetic factors associated with an increased risk of in-stent restenosis following stent placement for obstructive CAD. This review will also address genetic factors associated with in-stent restenosis, which may ultimately guide clinical decision-making regarding revascularization strategies for patients with CAD and MI.
Core tip: This review provides the most comprehensive summary of the genetics of coronary artery disease (CAD) and myocardial infarction (MI) research with a complete, up-to-date chromosomal map of all CAD and MI-susceptible genes. We discuss the existence and significance of protective genetic factors against atherosclerosis, CAD and MI. We also summarize the current status of constructing genetic risk scores to predict long-term risks of developing CAD and MI. In-stent restenosis is a new challenge in cardiology. The genetics of in-stent restenosis are also discussed in this article.