title: The gain-of-function variant allele CYP2C19*17: a double-edged sword between thrombosis and bleeding in clopidogrel-treated patients.
abstract: BACKGROUND
  A large number of clinical studies have documented that a loss-of-function variant CYP2C19*2 affects clinical profiles of clopidogrel (efficacy and safety). However, data on the impact of a gain-of-function variant CYP2C19*17 on the response to that drug seem to be less consistent.
  
  
  OBJECTIVE
  To systematically summarize all available clinical data assessing the role of the CYP2C19*17 variant in patients taking clopidogrel.
  
  
  METHODS
  A literature search was conducted and a meta-analysis was performed for 11 eligible studies. The endpoints included the major adverse cardiovascular events (MACE, representing non-fatal myocardial infarction, stroke, revascularization, or death), bleeding events, mortality, stent thrombosis and high platelet reactivity (HPR).
  
  
  RESULTS
  Data from six clinical studies demonstrated that carriers of the CYP2C19*17 variant had a marked protection against recurrent cardiovascular events in patients with coronary artery disease compared with non-carriers, as measured by a 16% decrease in the incidence of MACE (10.0% vs. 11.9%; OR, 0.82; 95% CI, 0.72-0.94; P = 0.005). On the other hand, carriers had an increased risk of developing bleeding as expected (8.0% vs. 6.5%; OR, 1.25; 95% CI, 1.07-1.47; P = 0.006; four studies). Moreover, the presence of the CYP2C19*17 variant might lead to increased response to clopidogrel, as shown by a marked lower prevalence of HPR in carriers than in non-carriers (37.9% vs. 50.8%; OR, 0.60; 95% CI, 0.45-0.79; P = 0.0003; three studies).
  
  
  CONCLUSIONS
  Carriers of the CYP2C19*17 variant have greater therapeutic responsiveness to clopidogrel than non-carriers, but they have an increased risk of developing bleeding as well.
authors: Therapeutic Drug Monitoring and Clinical Toxicology Center, Department of Pharmacy, Peking University Third Hospital, Beijing, China.
authors: Y
authors: Y
authors: Li
authors: H-L
authors: HL
authors: Tang
authors: Y-F
authors: YF
authors: Hu
authors: H-G
authors: HG
authors: Xie
mesh_terms: D001189:Aryl Hydrocarbon Hydroxylases / Q000235:genetics* / Q000378:metabolism; D000077144:Clopidogrel; D065731:Cytochrome P-450 CYP2C19; D020022:Genetic Predisposition to Disease; D014644:Genetic Variation; D006470:Hemorrhage / Q000139:chemically induced* / Q000201:enzymology / Q000235:genetics* / Q000401:mortality; D006801:Humans; D016017:Odds Ratio; D010641:Phenotype; D010975:Platelet Aggregation Inhibitors / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use*; D018570:Risk Assessment; D012307:Risk Factors; D013927:Thrombosis / Q000201:enzymology / Q000235:genetics* / Q000401:mortality / Q000517:prevention & control*; D013988:Ticlopidine / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000493:pharmacokinetics / Q000627:therapeutic use; D016896:Treatment Outcome
chemical_list: D010975:Platelet Aggregation Inhibitors; D000077144:Clopidogrel; D001189:Aryl Hydrocarbon Hydroxylases; C045793:CYP2C19 protein, human; D065731:Cytochrome P-450 CYP2C19; D013988:Ticlopidine