title: Effect of paraoxonase-1 polymorphism on clinical outcomes in patients treated with clopidogrel after an acute myocardial infarction.
abstract: Paraoxonase-1 (PON1) Q192R polymorphism was recently suggested to determine per se clopidogrel response on major cardiovascular events (MACEs). We assessed the impact of PON1, CYP2C19, and ABCB1 polymorphisms on MACE in clopidogrel-treated acute myocardial infarction (AMI) patients (N = 2,210), including those undergoing percutaneous coronary intervention (PCI) (n = 1,538). PON1 polymorphism was not associated with increased risk of in-hospital death and MACEs at 1 year (adjusted hazard ratio (HR) 1.03, 95% confidence interval (CI) 0.66-1.61 and adjusted HR 0.77, 95% CI 0.42-1.41 for QQ versus RR in all and PCI patients, respectively). The presence of two CYP2C19 loss-of-function (LOF) alleles was associated with the risk of in-hospital death and MACEs at 1 year in the overall population (adjusted odds ratio (OR) 3.67, 95% CI 1.05-12.80 and adjusted HR 1.96, 95% CI 1.08-3.54) and in PCI patients (adjusted OR 6.87, 95% CI 2.52-18.72 and adjusted HR 3.06, 95% CI 1.47-6.41). Unlike CYP2C19 polymorphism, PON1 (Q192R) polymorphism is not a major pharmacogenetic contributor of clinical response to clopidogrel in AMI patients.
authors.affiliation: Assistance Publique-Hôpitaux de Paris (APHP), Hôpital St. Antoine, URC-EST, Paris, France. tabassome.simon@sat.aphp.fr
authors.forename: T
authors.initials: T
authors.lastname: Simon
authors.forename: P G
authors.initials: PG
authors.lastname: Steg
authors.forename: L
authors.initials: L
authors.lastname: Becquemont
authors.forename: C
authors.initials: C
authors.lastname: Verstuyft
authors.forename: S
authors.initials: S
authors.lastname: Kotti
authors.forename: F
authors.initials: F
authors.lastname: Schiele
authors.forename: E
authors.initials: E
authors.lastname: Ferrari
authors.forename: E
authors.initials: E
authors.lastname: Drouet
authors.forename: G
authors.initials: G
authors.lastname: Grollier
authors.forename: N
authors.initials: N
authors.lastname: Danchin
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D043303:Aryldialkylphosphatase / Q000235:genetics*; D000077144:Clopidogrel; D005260:Female; D005500:Follow-Up Studies; D005838:Genotype; D017052:Hospital Mortality / Q000639:trends; D006801:Humans; D008297:Male; D008875:Middle Aged; D009203:Myocardial Infarction / Q000188:drug therapy* / Q000235:genetics* / Q000401:mortality; D011110:Polymorphism, Genetic / Q000235:genetics*; D011446:Prospective Studies; D012042:Registries; D013988:Ticlopidine / Q000031:analogs & derivatives* / Q000627:therapeutic use; D016896:Treatment Outcome
chemical_list: D000077144:Clopidogrel; D043303:Aryldialkylphosphatase; C468406:PON1 protein, human; D013988:Ticlopidine