title: Influence of CYP2C19 polymorphisms in platelet reactivity and prognosis in an unselected population of non ST elevation acute coronary syndrome.
abstract: OBJECTIVE
  CYP2C19*2 and CYP2C19*17 alleles appear to contribute to heterogeneous clopidogrel metabolism. The aims of the present study were to assess the phenotype-genotype relationship of CYP2C19*2 and *17 allele carriage and to explore the clinical impact of those polymorphisms at 6-month follow-up of an acute event in an unselected population of non-ST elevation acute coronary syndrome.
  
  
  METHODS
  Recruitment for the first and second objectives was 40 stable acute coronary syndrome patients under dual antiplatelet therapy at 12 months after coronary stent placement and an unselected population of 493 consecutive patients with non-ST elevation acute coronary syndrome, respectively. Platelet reactivity was assessed by optical aggregometry induced by adenosine diphosphate and thrombin receptor activating peptide, and by vasodilator-stimulated phosphoprotein phosphorylation measurement using flow cytometry. Genotypes were determined with a TaqMan assay.
  
  
  RESULTS
  Only the vasodilator-stimulated phosphoprotein phosphorylation measurement detected significant differences in on-clopidogrel platelet reactivity between the wild-type subjects and the CYP2C19*2 (P=.020) and *17 allele carriers (P=.048). No significant difference was found between CYP2C19*2 ([HR (95%CI): 1 (0.94-1.55)], P=.984) or *17 ([HR (95%CI): 0.93 (0.61-1.43)], P=.753) allele carriage and the occurrence of adverse events at 6-month follow-up.
  
  
  CONCLUSIONS
  Even though CYP2C19 genotype is associated with variable on-clopidogrel platelet reactivity, it has no significant clinical influence. Prognosis of acute coronary syndromes may be influenced by a myriad of variables.
authors: Servicio de Cardiología, Hospital Universitario Virgen de la Arrixaca, El Palmar, Murcia, Spain.
authors: Antonio
authors: A
authors: Tello-Montoliu
authors: Eva
authors: E
authors: Jover
authors: Francisco
authors: F
authors: Marín
authors: Agustina
authors: A
authors: Bernal
authors: María L
authors: ML
authors: Lozano
authors: Beatriz
authors: B
authors: Sánchez-Vega
authors: Francisco J
authors: FJ
authors: Pastor
authors: José A
authors: JA
authors: Hurtado
authors: Mariano
authors: M
authors: Valdés
authors: Vicente
authors: V
authors: Vicente
authors: José
authors: J
authors: Rivera
mesh_terms: D054058:Acute Coronary Syndrome / Q000097:blood / Q000201:enzymology / Q000235:genetics*; D000368:Aged; D001189:Aryl Hydrocarbon Hydroxylases / Q000235:genetics*; D000077144:Clopidogrel; D015331:Cohort Studies; D065731:Cytochrome P-450 CYP2C19; D005260:Female; D005500:Follow-Up Studies; D005838:Genotype; D006801:Humans; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D010641:Phenotype; D010750:Phosphoproteins / Q000378:metabolism; D010974:Platelet Aggregation / Q000187:drug effects; D010975:Platelet Aggregation Inhibitors / Q000627:therapeutic use*; D010979:Platelet Function Tests; D011110:Polymorphism, Genetic; D011379:Prognosis; D012044:Regression Analysis; D013988:Ticlopidine / Q000031:analogs & derivatives* / Q000627:therapeutic use
chemical_list: D010750:Phosphoproteins; D010975:Platelet Aggregation Inhibitors; D000077144:Clopidogrel; D001189:Aryl Hydrocarbon Hydroxylases; C045793:CYP2C19 protein, human; D065731:Cytochrome P-450 CYP2C19; D013988:Ticlopidine