title: Influence of CYP2C19 loss-of-function variants on the antiplatelet effects and cardiovascular events in clopidogrel-treated Chinese patients undergoing percutaneous coronary intervention.
abstract: OBJECTIVE
  A large number of clinical studies have well demonstrated that the loss-of-function variant allele CYP2C19 2 is associated with attenuated response to clopidogrel and increased risk of developing stent thrombosis (ST) in white or black patients with stenting. However, similar association studies on the effect of the CYP2C19 2 and 3 variants on maximum platelet aggregation (MPA) and the risk of cardiovascular events are currently unavailable for the Chinese patients. This work was aimed at assessing the impact of the CYP2C19 2 and 3 variants on the antiplatelet effects and adverse cardiovascular events in clopidogrel-treated Chinese patients undergoing percutaneous coronary intervention (PCI).
  
  
  METHODS
  The study population consisted of 617 patients undergoing PCI. Genotypes were determined using MALDI/TOF-MS. MPA was measured by light transmittance aggregometry. The clinical end-point was the 1-year incidence of adverse cardiovascular events, including ST.
  
  
  RESULTS
  Carriers of CYP2C19 heterozygous (1/2, or 1/3; n = 278) and mutant homozygous (2/2, 2/3, or 3/3, n = 80) genotypes had significantly higher MPA values than noncarriers (1/1; n = 259; P = 0.036 and 0.007 respectively). Moreover, the presence of the CYP2C19 2 or 3 mutant allele was significantly associated with an increased risk of developing ST, with the higher risk of ST being seen in patients homozygous for the CYP2C19 2 or 3 variant allele than in noncarriers (OR, 13.58; 95% CI, 1.49-123.31; P = 0.012). Furthermore, multivariate analysis revealed an independent association of the presence of CYP2C19*2 and/or 3 variant alleles with greater MPA values (P = 0.001) and increased risk of ST (OR, 11.67; 95% CI, 1.21-78.83; P = 0.022). However, there was no significant influence of CYP2C19 2 and 3 on the risk of developing other adverse cardiovascular events.
  
  
  CONCLUSIONS
  Carriage of the loss-of-function genetic variants CYP2C19 2 and 3 is significantly associated with attenuated platelet response to clopidogrel and an increased risk of ST in Chinese patients treated with stenting.
authors.affiliation: Key Laboratory of Drug Metabolism and Pharmacokinetics, China Pharmaceutical University, Nanjing 210009, China.
authors.forename: Jian-Jun
authors.initials: JJ
authors.lastname: Zou
authors.forename: Hong-Guang
authors.initials: HG
authors.lastname: Xie
authors.forename: Shao-Liang
authors.initials: SL
authors.lastname: Chen
authors.forename: Jie
authors.initials: J
authors.lastname: Tan
authors.forename: Ling
authors.initials: L
authors.lastname: Lin
authors.forename: Ying-Ying
authors.initials: YY
authors.lastname: Zhao
authors.forename: Hai-Mei
authors.initials: HM
authors.lastname: Xu
authors.forename: Song
authors.initials: S
authors.lastname: Lin
authors.forename: Juan
authors.initials: J
authors.lastname: Zhang
authors.forename: Guang-Ji
authors.initials: GJ
authors.lastname: Wang
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D001189:Aryl Hydrocarbon Hydroxylases / Q000235:genetics*; D044466:Asian People; D002681:China; D000077144:Clopidogrel; D003328:Coronary Thrombosis / Q000201:enzymology / Q000209:etiology / Q000235:genetics* / Q000517:prevention & control; D065731:Cytochrome P-450 CYP2C19; D004247:DNA / Q000235:genetics; D005260:Female; D005838:Genotype; D006331:Heart Diseases / Q000201:enzymology / Q000209:etiology / Q000235:genetics* / Q000517:prevention & control; D006801:Humans; D016014:Linear Models; D008297:Male; D008875:Middle Aged; D062645:Percutaneous Coronary Intervention / Q000009:adverse effects; D010974:Platelet Aggregation / Q000187:drug effects / Q000235:genetics; D010975:Platelet Aggregation Inhibitors / Q000493:pharmacokinetics / Q000627:therapeutic use*; D011110:Polymorphism, Genetic; D011446:Prospective Studies; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; D015607:Stents; D013988:Ticlopidine / Q000031:analogs & derivatives* / Q000493:pharmacokinetics / Q000627:therapeutic use; D055815:Young Adult
chemical_list: D010975:Platelet Aggregation Inhibitors; D004247:DNA; D000077144:Clopidogrel; D001189:Aryl Hydrocarbon Hydroxylases; C045793:CYP2C19 protein, human; D065731:Cytochrome P-450 CYP2C19; D013988:Ticlopidine