title: CYP2C19 and nongenetic factors predict poor responsiveness to clopidogrel loading dose after coronary stent implantation.
abstract: OBJECTIVE
  To investigate an association of responsiveness to clopidogrel loading dose with genotypes of cytochrome P450 (CYP) 2C19, other CYP isozymes and nongenetic factors in patients with coronary artery disease.
  
  
  METHODS
  Genotyping for CYP2C19 (*2, *3 and *17), CYP3A4*1B and CYP3A5*3 variants was performed in patients (n = 237) who underwent percutaneous coronary intervention. Adenosine diphosphate-induced platelet aggregation was determined after first administration of 600 mg clopidogrel.
  
  
  RESULTS
  CYP2C19*2 carriers showed significantly increased residual platelet aggregation (RPA) (OR: 4.6; 95% CI: 2.5-8.7; p < 0.0001) compared with noncarriers. All other polymorphisms had no influence on RPA. For the development of a risk score for better prediction of RPA, CYP2C19*2 genotype and previously identified nongenetic risk factors (age >65 years, Type 2 diabetes mellitus, decreased left ventricular function, renal failure and acute coronary syndrome) were analyzed. Multivariable logistic regression analysis showed a significant correlation of the nongenetic factors (chi (2) = 5.32; p = 0.021) and CYP2C19*2 (chi (2) = 21.31; p < 0.0001) with high RPA, and an even higher association for the combination of both (chi (2) = 25.85; p < 0.0001).
  
  
  CONCLUSIONS
  Prediction of responsiveness after clopidogrel loading dose may substantially be improved by adding CYP2C19*2 genotype to nongenetic risk factors.
authors.affiliation: Department of Cardiology, University Hospital Tuebingen, Otfried-Mueller-Strasse 10, Tuebingen, Germany. meinrad.gawaz@med.uni-tuebingen.de
authors.forename: Tobias
authors.initials: T
authors.lastname: Geisler
authors.forename: Elke
authors.initials: E
authors.lastname: Schaeffeler
authors.forename: Juergen
authors.initials: J
authors.lastname: Dippon
authors.forename: Stefan
authors.initials: S
authors.lastname: Winter
authors.forename: Verena
authors.initials: V
authors.lastname: Buse
authors.forename: Christian
authors.initials: C
authors.lastname: Bischofs
authors.forename: Christine
authors.initials: C
authors.lastname: Zuern
authors.forename: Klaus
authors.initials: K
authors.lastname: Moerike
authors.forename: Meinrad
authors.initials: M
authors.lastname: Gawaz
authors.forename: Matthias
authors.initials: M
authors.lastname: Schwab
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D001189:Aryl Hydrocarbon Hydroxylases / Q000235:genetics*; D006348:Cardiac Surgical Procedures / Q000295:instrumentation / Q000639:trends*; D000077144:Clopidogrel; D003324:Coronary Artery Disease / Q000097:blood / Q000235:genetics / Q000601:surgery; D065731:Cytochrome P-450 CYP2C19; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D011237:Predictive Value of Tests; D012307:Risk Factors; D015607:Stents; D013988:Ticlopidine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000097:blood
chemical_list: D000077144:Clopidogrel; D001189:Aryl Hydrocarbon Hydroxylases; C045793:CYP2C19 protein, human; D065731:Cytochrome P-450 CYP2C19; D013988:Ticlopidine