title: Effect of the CYP2C19 2 and 3 genotypes, ABCB1 C3435T and PON1 Q192R alleles on the pharmacodynamics and adverse clinical events of clopidogrel in Chinese people after percutaneous coronary intervention.
abstract: OBJECTIVE
  Chinese people are more frequent carriers of cytochrome P450 2C19 (CYP2C19) loss-of-function alleles than Caucasians. The effect of the ATP-binding cassette, sub-family B, member 1 (ABCB1), and paraoxonase 1 (PON1) variants on platelet reactivity and clinical outcomes of clopidogrel treatment has not yet been reported in Chinese patients after percutaneous coronary intervention. The aim of this study was to investigate the effect of the CYP2C19, ABCB1, and PON1 variants on clopidogrel pharmacodynamics and clinical outcomes in these patients.
  
  
  METHODS
  Six hundred and seventy patients after percutaneous coronary intervention were enrolled in a single-center registry. The antiplatelet effect of clopidogrel was assessed by thromboelastography, and the CYP2C19, ABCB1, and PON1 genotypes were detected by the ligase detection reaction. Primary clinical endpoints included cardiovascular death, nonfatal myocardial infarction, target vessel revascularization, and stent thrombosis. The secondary clinical endpoints were thrombolysis in myocardial infarction bleeding. The follow-up period was 12 months.
  
  
  RESULTS
  The frequency of the CYP2C19 loss-of-function alleles was relatively high (57.3 %). The risk of a low response to clopidogrel and composite ischemic events increased with the number of CYP2C19 loss-of-function alleles. However, there were not significant differences in clopidogrel pharmacodynamics and clinical outcomes across the ABCB1 and PON1 genotype groups; bleeding was not significantly different across the CYP2C19, ABCB1, and PON1 genotype groups.
  
  
  CONCLUSIONS
  The CYP2C19 loss-of-function alleles had a gene dose effect on the pharmacodynamics and composite ischemic events of clopidogrel in our study population. Neither the ABCB1 nor the PON1 genotype significantly influenced the antiplatelet effect and clinical outcomes of clopidogrel in these patients.
authors.affiliation: Department of Cardiology, Fuwai Hospital and Cardiovascular Institute, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100037, China.
authors.forename: Xiao-Fang
authors.initials: XF
authors.lastname: Tang
authors.forename: Jing
authors.initials: J
authors.lastname: Wang
authors.forename: Jia-Hui
authors.initials: JH
authors.lastname: Zhang
authors.forename: Xian-Min
authors.initials: XM
authors.lastname: Meng
authors.forename: Bo
authors.initials: B
authors.lastname: Xu
authors.forename: Shu-Bin
authors.initials: SB
authors.lastname: Qiao
authors.forename: Yong-Jian
authors.initials: YJ
authors.lastname: Wu
authors.forename: Jue
authors.initials: J
authors.lastname: Chen
authors.forename: Yuan
authors.initials: Y
authors.lastname: Wu
authors.forename: Ji-Lin
authors.initials: JL
authors.lastname: Chen
authors.forename: Run-Lin
authors.initials: RL
authors.lastname: Gao
authors.forename: Jin-Qing
authors.initials: JQ
authors.lastname: Yuan
authors.forename: Yue-Jin
authors.initials: YJ
authors.lastname: Yang
mesh_terms: D018435:ATP Binding Cassette Transporter, Subfamily B; D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000235:genetics*; D000483:Alleles; D001189:Aryl Hydrocarbon Hydroxylases / Q000235:genetics*; D043303:Aryldialkylphosphatase / Q000235:genetics*; D044466:Asian People / Q000235:genetics; D000077144:Clopidogrel; D065731:Cytochrome P-450 CYP2C19; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D062645:Percutaneous Coronary Intervention; D010974:Platelet Aggregation / Q000187:drug effects / Q000235:genetics; D010975:Platelet Aggregation Inhibitors / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use; D020641:Polymorphism, Single Nucleotide; D012042:Registries; D013988:Ticlopidine / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use
chemical_list: C513055:ABCB1 protein, human; D018435:ATP Binding Cassette Transporter, Subfamily B; D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D010975:Platelet Aggregation Inhibitors; D000077144:Clopidogrel; D001189:Aryl Hydrocarbon Hydroxylases; C045793:CYP2C19 protein, human; D065731:Cytochrome P-450 CYP2C19; D043303:Aryldialkylphosphatase; C468406:PON1 protein, human; D013988:Ticlopidine