Genetics of response to antiplatelet therapy

Research output: Contribution to journalArticle

Authors

Colleges, School and Institutes

External organisations

  • University of Sheffield

Abstract

Dual antiplatelet therapy has a major role in the management of acute coronary syndromes (ACS) and following percutaneous coronary intervention (PCI). However, significant variation in pharmacodynamic response to antiplatelet therapy has been demonstrated, especially to clopidogrel. Single nucleotide polymorphisms, particularly those affecting the metabolism of antiplatelet therapy, account for some, but not all, of this variability in response. Loss-of-function polymorphisms of CYP2C19, the gene encoding for the key enzyme in the metabolism of clopidogrel, are associated with reduced formation of the active metabolite of clopidogrel, a lower pharmacodynamic effect of the drug and a corresponding increase in adverse cardiovascular events. Conversely, gain-of-function polymorphisms of CYP2C19 are associated with an increased pharmacodynamic response to the drug and therefore an increase in bleeding. The clinical relevance of other polymorphisms that affect antiplatelet therapy has not been clearly established.

Details

Original languageEnglish
Pages (from-to)123-53
Number of pages31
JournalProgress in molecular biology and translational science
Volume124
Publication statusPublished - 2014

Keywords

  • Animals, Humans, Pharmacogenetics, Platelet Aggregation Inhibitors, Treatment Outcome, Journal Article, Review