title: Relationship of CYP2C19*2 and CYP2C19*3 gene polymorphism with clopidogrel response variability and recurrent cardiovascular events in Chinese patients undergoing percutaneous coronary intervention.
abstract: OBJECTIVE
  The study was conducted to assess the influence of CYP2C19 polymorphisms on clopidogrel response variability and recurrent cardiovascular (CV) events in Chinese patients undergoing percutaneous coronary intervention (PCI).
  
  
  METHODS
  Platelet aggregation induced by 5 and 20 µmol/l adenosine diphosphate was measured in 109 patients at baseline, 12 h and 36 h after loading with 300 mg of clopidogrel. The primary end point was recurrent CV events, and the follow-up was scheduled at 1, 3, 6 and 12 months after PCI. The polymorphisms of CYP2C19*2 and CYP2C19*3 were genotyped by DNA sequencing analysis.
  
  
  RESULTS
  The maximal aggregation rates and inhibition of platelet aggregation among CYP2C19*1/*1, CYP2C19*1/*2 or *3 and CYP2C19*2/*2 or *3 genotypes were significantly different at 12 and 36 h after clopidogrel loading dose administration. Multiple linear regression analysis demonstrated that CYP2C19*2 and CYP2C19*3 might be predictors of clopidogrel response variability. During the 12-month follow-up, recurrent CV events occurred in 21 (19.63%) patients, and there were 5 (6.47%) deaths, 3 (2.80%) cases of ischemic stroke and 14 (13.1%) cases of acute coronary syndrome. Carriers of at least one CYP2C19 loss-of-function allele (*1/*2 or *3, *2/*2 or *3) incurred a 3.65-fold increase (95% CI 1.07-12.38; p = 0.038) in the risk of recurrent CV events 1 year after PCI compared to noncarriers (*1/*1).
  
  
  CONCLUSIONS
  Polymorphisms in CYP2C19*2 and CYP2C19*3 contribute to variabilities in clopidogrel responsiveness. Patients carrying at least one CYP2C19 loss-of-function allele (CYP2C19*2, *3) are associated with an increased risk of recurrent CV events undergoing PCI.
authors: Laboratory of Pharmacy, Zhongda Hospital, Southeast University, Nanjing, China.
authors: Yamin
authors: Y
authors: Liu
authors: Naifeng
authors: N
authors: Liu
authors: Weilan
authors: W
authors: Li
authors: Hua
authors: H
authors: Shao
authors: Hong
authors: H
authors: Zhi
authors: Jie
authors: J
authors: Li
mesh_terms: D000368:Aged; D001189:Aryl Hydrocarbon Hydroxylases / Q000235:genetics*; D044466:Asian People / Q000235:genetics; D002318:Cardiovascular Diseases / Q000453:epidemiology / Q000235:genetics* / Q000517:prevention & control; D000077144:Clopidogrel; D065731:Cytochrome P-450 CYP2C19; D005260:Female; D005787:Gene Frequency; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D062645:Percutaneous Coronary Intervention; D010975:Platelet Aggregation Inhibitors / Q000627:therapeutic use*; D011110:Polymorphism, Genetic; D058921:Purinergic P2Y Receptor Antagonists / Q000627:therapeutic use*; D013988:Ticlopidine / Q000031:analogs & derivatives* / Q000627:therapeutic use; D016896:Treatment Outcome
chemical_list: D010975:Platelet Aggregation Inhibitors; D058921:Purinergic P2Y Receptor Antagonists; D000077144:Clopidogrel; D001189:Aryl Hydrocarbon Hydroxylases; C045793:CYP2C19 protein, human; D065731:Cytochrome P-450 CYP2C19; D013988:Ticlopidine