title: The pharmacogenetic control of antiplatelet response: candidate genes and CYP2C19.
abstract: BACKGROUND
  Aspirin, clopidogrel, prasugrel and ticagrelor are antiplatelet agents for the prevention of ischemic events in patients with acute coronary syndromes (ACS), percutaneous coronary intervention (PCI) and other indications. Variability in response is observed to different degrees with these agents, which can translate to increased risks for adverse cardiovascular events. As such, potential pharmacogenetic determinants of antiplatelet pharmacokinetics, pharmacodynamics and clinical outcomes have been actively studied.
  
  
  METHODS
  This article provides an overview of the available antiplatelet pharmacogenetics literature. Evidence supporting the significance of candidate genes and their potential influence on antiplatelet response and clinical outcomes are summarized and evaluated. Additional focus is directed at CYP2C19 and clopidogrel response, including the availability of clinical testing and genotype-directed antiplatelet therapy.
  
  
  CONCLUSIONS
  The reported aspirin response candidate genes have not been adequately replicated and few candidate genes have thus far been implicated in prasugrel or ticagrelor response. However, abundant data support the clinical validity of CYP2C19 and clopidogrel response variability among ACS/PCI patients. Although limited prospective trial data are available to support the utility of routine CYP2C19 testing, the increased risks for reduced clopidogrel efficacy among ACS/PCI patients that carry CYP2C19 loss-of-function alleles should be considered when genotype results are available.
authors.affiliation: a 1 Icahn School of Medicine at Mount Sinai, Department of Genetics and Genomic Sciences , New York, NY, USA +1 212 241 3780 ; +1 212 241 0139 ; stuart.scott@mssm.edu.
authors.forename: Yao
authors.initials: Y
authors.lastname: Yang
authors.affiliation: b 2 University of Maryland School of Medicine, Division of Endocrinology, Diabetes and Nutrition, and Program for Personalized and Genomic Medicine , Baltimore, MD, USA.
authors.forename: Joshua P
authors.initials: JP
authors.lastname: Lewis
authors.affiliation: c 3 Icahn School of Medicine at Mount Sinai, Cardiovascular Research Center , New York, NY, USA.|d 4 Sorbonne Universités, UPMC Univ Paris 06, INSERM , UMR_S 1166 ICAN, F-75005 Paris, France.
authors.forename: Jean-Sébastien
authors.initials: JS
authors.lastname: Hulot
authors.affiliation: a 1 Icahn School of Medicine at Mount Sinai, Department of Genetics and Genomic Sciences , New York, NY, USA +1 212 241 3780 ; +1 212 241 0139 ; stuart.scott@mssm.edu.
authors.forename: Stuart A
authors.initials: SA
authors.lastname: Scott
mesh_terms: D002318:Cardiovascular Diseases / Q000453:epidemiology / Q000209:etiology; D000077144:Clopidogrel; D065731:Cytochrome P-450 CYP2C19 / Q000235:genetics* / Q000378:metabolism; D005838:Genotype; D006801:Humans; D010597:Pharmacogenetics; D010975:Platelet Aggregation Inhibitors / Q000009:adverse effects / Q000493:pharmacokinetics* / Q000494:pharmacology; D013988:Ticlopidine / Q000008:administration & dosage / Q000031:analogs & derivatives / Q000493:pharmacokinetics / Q000494:pharmacology
chemical_list: D010975:Platelet Aggregation Inhibitors; D000077144:Clopidogrel; D065731:Cytochrome P-450 CYP2C19; D013988:Ticlopidine
keywords: CYP2C19; antiplatelet agents; aspirin; candidate genes; clopidogrel; pharmacogenetics; pharmacogenomics; prasugrel; ticagrelor