title: Effect of cytochrome p450 polymorphisms on platelet reactivity after treatment with clopidogrel in acute coronary syndrome.
abstract: Genetic polymorphisms of cytochrome P450 (CYP) isoforms may promote variability in platelet response to clopidogrel. This study was conducted to analyze, in 603 patients with non-ST elevation acute coronary syndromes, the effect of CYP3A4, CYP3A5, and CYP2C19 gene polymorphisms on clopidogrel response and post-treatment platelet reactivity assessed by adenosine diphosphate (ADP)-induced platelet aggregation, vasodilator-stimulated phosphoprotein phosphorylation index, and ADP-induced P-selectin expression. The CYP2C19*2 polymorphism was significantly associated with ADP-induced platelet aggregation, vasodilator-stimulated phosphoprotein phosphorylation index, and ADP-induced P-selectin expression in recessive (p <0.01, p <0.007, and p <0.06, respectively) and codominant (p <0.08, p <0.0001, and p <0.009, respectively) models, but the CYP3A4*1B and CYP3A5*3 polymorphisms were not. The CYP2C19*2 allele carriers exhibited the highest platelet index levels in multivariate analysis (p = 0.03). After covariate adjustment, the CYP2C19*2 allele was more frequent in clopidogrel nonresponders, defined by persistent high post-treatment platelet reactivity (ADP-induced platelet aggregation >70%; p = 0.03). In conclusion, the present data suggest that the CYPC19*2 allele influences post-treatment platelet reactivity and clopidogrel response in patients with non-ST elevation acute coronary syndromes.
authors.affiliation: INSERM U626, Marseille, France.
authors.forename: Corinne
authors.initials: C
authors.lastname: Frere
authors.forename: Thomas
authors.initials: T
authors.lastname: Cuisset
authors.forename: Pierre-Emmanuel
authors.initials: PE
authors.lastname: Morange
authors.forename: Jacques
authors.initials: J
authors.lastname: Quilici
authors.forename: Laurence
authors.initials: L
authors.lastname: Camoin-Jau
authors.forename: Noémie
authors.initials: N
authors.lastname: Saut
authors.forename: Dorothee
authors.initials: D
authors.lastname: Faille
authors.forename: Marc
authors.initials: M
authors.lastname: Lambert
authors.forename: Irène
authors.initials: I
authors.lastname: Juhan-Vague
authors.forename: Jean-Louis
authors.initials: JL
authors.lastname: Bonnet
authors.forename: Marie-Christine
authors.initials: MC
authors.lastname: Alessi
mesh_terms: D054058:Acute Coronary Syndrome / Q000188:drug therapy*; D000244:Adenosine Diphosphate; D000483:Alleles; D015992:Body Mass Index; D015815:Cell Adhesion Molecules / Q000378:metabolism; D000077144:Clopidogrel; D003577:Cytochrome P-450 Enzyme System / Q000235:genetics*; D004351:Drug Resistance / Q000235:genetics; D005260:Female; D006579:Heterozygote; D006801:Humans; D008297:Male; D008840:Microfilament Proteins / Q000378:metabolism; D008875:Middle Aged; D019007:P-Selectin / Q000378:metabolism; D010750:Phosphoproteins / Q000378:metabolism; D010766:Phosphorylation; D015539:Platelet Activation / Q000235:genetics*; D010975:Platelet Aggregation Inhibitors / Q000627:therapeutic use*; D020641:Polymorphism, Single Nucleotide; D011446:Prospective Studies; D013988:Ticlopidine / Q000031:analogs & derivatives* / Q000627:therapeutic use; D000098662:Vasodilator-Stimulated Phosphoprotein
chemical_list: D015815:Cell Adhesion Molecules; D008840:Microfilament Proteins; D019007:P-Selectin; D010750:Phosphoproteins; D010975:Platelet Aggregation Inhibitors; D000098662:Vasodilator-Stimulated Phosphoprotein; D000244:Adenosine Diphosphate; D003577:Cytochrome P-450 Enzyme System; D000077144:Clopidogrel; D013988:Ticlopidine