title: [Relevance of CYP2C19 2 regarding platelet reactivity in patients with acute coronary syndrome treated with clopidogrel].
abstract: OBJECTIVE
  Previous studies have shown that the metabolism of P2Y12 receptor blockers is influenced not only by CYP2C19 2 but also by PON1-Q192R alelles. We aimed to evaluate the impact of CYP2C19 2 and PON1-Q192R polymorphisms carriage in platelet reactivity and clinical outcome in patients with ischemic heart disease undergoing cardiac catheterization.
  
  
  METHODS
  We recruited prospectively patients with acute coronary syndrome undergoing cardiac catheterization (n=247). We evaluated the genotype (CYP2C19 2, CYP2C19 17, PON1-Q192R) with TaqMan(®) assay and platelet aggregometry in all patients. We assessed both in and out-of-hospital events (unstable angina, periprocedural and spontaneous myocardial infarction, myocardial infarction, all-cause death, stent thrombosis and stroke) during follow-up.
  
  
  RESULTS
  Carriers of CYP2C19 2 alleles showed a significant higher residual platelet reactivity (PRU, mean [SD], 252 [76] vs. 287 [74], P=.002). Carriers of PON1-Q192R CT(RQ) and TT(QQ) alleles and CYP2C19 17 did not present a different response to clopidogrel. In a multivariable setting for the prediction of platelet reactivity, the contribution of CYP2C19 2 was modest (Wald=7.5; odds ratio [OR] for ≥ 1 alelle 2=2,786, 95% confidence interval [95% CI] 1,337-5,808). Independent predictors were baseline hemoglobin levels (g/dL, OR .666, 95% CI .555-.801) and the use of statins (OR .376, 95% CI .162-.873). Body mass index was a risk factor (OR 1,074, CI 95% 1,005-1,148). Studied polymorphisms did not predict an adverse outcome.
  
  
  CONCLUSIONS
  CYP2C19 2 polymorphism influenced moderately platelet reactivity but did not show an impact on clinical outcome in patients with acute coronary syndrome. Neither CYP2C19 17 nor PON1-Q192R polymorphisms showed an impact upon platelet reactivity or outcome.
authors.affiliation: Servicio de Cardiología, Hospital General Universitario de Santa Lucía, Cartagena, Murcia, España.
authors.forename: Pedro
authors.initials: P
authors.lastname: Cano
authors.affiliation: Servicio de Cardiología, Hospital General Universitario de Santa Lucía, Cartagena, Murcia, España. Electronic address: lconsue@gmail.com.
authors.forename: Luciano
authors.initials: L
authors.lastname: Consuegra-Sánchez
authors.affiliation: Servicio de Anatomía Patológica, Hospital General Universitario de Santa Lucía, Cartagena, Murcia, España.
authors.forename: Pablo
authors.initials: P
authors.lastname: Conesa
authors.affiliation: Servicio de Cardiología, Hospital General Universitario de Santa Lucía, Cartagena, Murcia, España.
authors.forename: Daniel
authors.initials: D
authors.lastname: Torres-Moreno
authors.affiliation: Servicio de Cardiología, Hospital General Universitario de Santa Lucía, Cartagena, Murcia, España.
authors.forename: Leticia
authors.initials: L
authors.lastname: Jaulent
authors.affiliation: Servicio de Cardiología, Hospital General Universitario de Santa Lucía, Cartagena, Murcia, España.
authors.forename: Derek
authors.initials: D
authors.lastname: Dau
authors.affiliation: Servicio de Cardiología, Hospital General Universitario de Santa Lucía, Cartagena, Murcia, España.
authors.forename: Francisco
authors.initials: F
authors.lastname: Picó
authors.affiliation: Servicio de Cardiología, Hospital General Universitario de Santa Lucía, Cartagena, Murcia, España.
authors.forename: Manuel
authors.initials: M
authors.lastname: Villegas
mesh_terms: D054058:Acute Coronary Syndrome / Q000097:blood / Q000188:drug therapy / Q000235:genetics*; D000368:Aged; D000483:Alleles; D000789:Angina, Unstable / Q000453:epidemiology; D043303:Aryldialkylphosphatase / Q000235:genetics / Q000502:physiology; D001711:Biotransformation / Q000235:genetics; D006328:Cardiac Catheterization; D000077144:Clopidogrel; D003328:Coronary Thrombosis / Q000453:epidemiology; D065731:Cytochrome P-450 CYP2C19 / Q000235:genetics / Q000502:physiology*; D005260:Female; D005500:Follow-Up Studies; D005838:Genotype; D017052:Hospital Mortality; D006801:Humans; D015994:Incidence; D008297:Male; D008875:Middle Aged; D009203:Myocardial Infarction / Q000453:epidemiology; D010974:Platelet Aggregation / Q000187:drug effects / Q000235:genetics*; D010975:Platelet Aggregation Inhibitors / Q000493:pharmacokinetics* / Q000494:pharmacology / Q000627:therapeutic use; D020641:Polymorphism, Single Nucleotide; D011379:Prognosis; D011446:Prospective Studies; D058921:Purinergic P2Y Receptor Antagonists / Q000493:pharmacokinetics* / Q000494:pharmacology / Q000627:therapeutic use; D012307:Risk Factors; D015607:Stents / Q000009:adverse effects; D020521:Stroke / Q000453:epidemiology; D016019:Survival Analysis; D013988:Ticlopidine / Q000031:analogs & derivatives* / Q000493:pharmacokinetics / Q000494:pharmacology / Q000627:therapeutic use
chemical_list: D010975:Platelet Aggregation Inhibitors; D058921:Purinergic P2Y Receptor Antagonists; D000077144:Clopidogrel; D065731:Cytochrome P-450 CYP2C19; D043303:Aryldialkylphosphatase; C468406:PON1 protein, human; D013988:Ticlopidine
keywords: Aggregometry; Agregometría; Genetics; Genética; Ischemic cardiac disease; Isquemia miocárdica; Plaquetas; Platelets