title: Genetics of response to antiplatelet therapy.
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.
authors.affiliation: Department of Cardiovascular Science, University of Sheffield, Sheffield, United Kingdom.
authors.forename: Mark R
authors.initials: MR
authors.lastname: Thomas
authors.affiliation: Department of Cardiovascular Science, University of Sheffield, Sheffield, United Kingdom.
authors.forename: Robert F
authors.initials: RF
authors.lastname: Storey
mesh_terms: D000818:Animals; D006801:Humans; D010597:Pharmacogenetics; D010975:Platelet Aggregation Inhibitors / Q000627:therapeutic use*; D016896:Treatment Outcome
chemical_list: D010975:Platelet Aggregation Inhibitors
keywords: Acute coronary syndromes; Antiplatelet therapy; Aspirin; Clopidogrel; GPIIb/IIIa inhibitors; Pharmacogenomics; Prasugrel; Ticagrelor