Molecular Genetics of Myocardial Infarction

Yoshiji Yamada, Mie University, Tsu, Japan

Published online: February 2010

DOI: 10.1002/9780470015902.a0022412

Myocardial infarction (MI) is an important clinical problem because of its large contribution to mortality. The main causal and treatable risk factors for MI include hypertension, dyslipidaemia, diabetes mellitus, chronic kidney disease and smoking. In addition to these risk factors, recent studies have shown the importance of genetic factors and interactions between multiple genes and environmental factors. Genetic linkage analyses of families and sib-pairs as well as candidate gene association studies have implicated several loci and many candidate genes in predisposition to coronary heart disease (CHD) or MI. Recent genome-wide association studies demonstrated that single nucleotide polymorphisms (SNPs) at chromosome 9p21.3 or other loci were associated with CHD or MI. Such studies may provide insight into the function of implicated genes as well as into the role of genetic factors in the development of CHD and MI.

Key concepts

  • Twin and family studies have established that CHD aggregates in families, with a family history of early onset CHD being considered a risk factor for the disease.
  • Genes responsible for familial hypercholesterolaemia and Tangier disease are the prototypical examples of causal genes for Mendelian disorders associated with CHD and MI.
  • Several genome-wide linkage analyses of families or sib-pairs have identified chromosomal loci linked, or genetic variations that confer susceptibility, to MI, acute coronary syndrome (ACS) or CHD.
  • Various association studies of unrelated individuals have identified genetic variations that confer susceptibility to MI or CHD. Numerous candidate genes have been implicated, but those that show reproducible associations between risk alleles and CHD or MI in replication studies are few.
  • A genome-wide association study (GWAS) and subsequent analysis have suggested that the lymphotoxin alpha gene is important in the pathogenesis of coronary atherosclerosis and thrombosis.
  • Four independent GWAS have identified SNPs at chromosome 9p21.3 that were associated with CHD or MI in several white cohorts.
  • In addition, several GWAS identified SNPs associated with CHD or MI at various chromosomal loci.
  • Identification of susceptibility genes for CHD and MI and clarification of the functional relevance of genetic variants to these conditions will contribute to the prevention, early diagnosis and treatment of CHD and MI.

Keywords: myocardial infarction; coronary heart disease; genetics; polymorphism; linkage analysis; genome-wide association study

Figure 1. Pathogenesis of myocardial infarction. The main causal and treatable risk factors for MI include hypertension, diabetes mellitus, dyslipidaemia, chronic kidney disease and smoking. In addition to these risk factors, genetic factors and interactions between multiple genes and environmental factors are important in the development of myocardial infarction.
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Related Sub-Topics:

Molecular Genetics of Common and Complex Disease | Specific Genetic Disorders | Linkage Analysis | Gene Mapping by Disease Association
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Article Title: Molecular Genetics of Myocardial Infarction
 
How to Cite close
Yamada, Yoshiji(Feb 2010) Molecular Genetics of Myocardial Infarction. In: eLS. John Wiley & Sons Ltd, Chichester. http://www.els.net [doi: 10.1002/9780470015902.a0022412]