title: Effects of CYP2C19 variant alleles on postclopidogrel platelet reactivity and clinical outcomes in an actual clinical setting in China.
abstract: Whether the current pharmacogenetic knowledge of clopidogrel could be translated into Chinese clinical practice is yet to be defined. To address this issue, we assessed the relation of single nucleotide polymorphisms within genes modulating clopidogrel absorption (ABCB1), metabolic activation (CYP2B6, CYP2D6, CYP3A4, CYP2C9, and CYP2C19), and biologic activity (P2RY12) to the response of clopidogrel as measured by ex-vivo platelet reactivity and ischemic events during half a year of follow-up. Only CYP2C19*2 and *3, of the investigated polymorphisms, were associated with postclopidogrel platelet aggregation and the presence of high platelet reactivity. Moreover, the effect of the CYP2C19*2 versus the *3 allele on platelet reactivity did not differ. Although the carriage of one or two CYP2C19 loss-of-function alleles, irrespective of the CYP2C19*2 or *3 allele, increased the propensity for high platelet reactivity, only the two loss-of-function allele carriage was associated with clinical outcome in the first 6 months.
authors.affiliation: Department of Cardiology, Shanghai Institute of Cardiovascular Diseases, Zhongshan Hospital bFudan-VARI Center for Genetic Epidemiology, School of Life Science, Fudan University, Shanghai, China.
authors.forename: Hongyi
authors.initials: H
authors.lastname: Wu
authors.forename: Juying
authors.initials: J
authors.lastname: Qian
authors.forename: Jianfeng
authors.initials: J
authors.lastname: Xu
authors.forename: Aijun
authors.initials: A
authors.lastname: Sun
authors.forename: Wenzhu
authors.initials: W
authors.lastname: Sun
authors.forename: Qibing
authors.initials: Q
authors.lastname: Wang
authors.forename: Junbo
authors.initials: J
authors.lastname: Ge
mesh_terms: D000483:Alleles; D001189:Aryl Hydrocarbon Hydroxylases / Q000235:genetics*; D001792:Blood Platelets / Q000187:drug effects*; D002681:China; D000077144:Clopidogrel; D065731:Cytochrome P-450 CYP2C19; D005838:Genotype; D006801:Humans; D017202:Myocardial Ischemia / Q000097:blood / Q000188:drug therapy; D010974:Platelet Aggregation / Q000187:drug effects*; D010975:Platelet Aggregation Inhibitors / Q000494:pharmacology* / Q000627:therapeutic use; D020641:Polymorphism, Single Nucleotide; D013988:Ticlopidine / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use
chemical_list: D010975:Platelet Aggregation Inhibitors; D000077144:Clopidogrel; D001189:Aryl Hydrocarbon Hydroxylases; C045793:CYP2C19 protein, human; D065731:Cytochrome P-450 CYP2C19; D013988:Ticlopidine