title: Effect of CYP2C19*2 and *3 on clinical outcome in ischemic stroke patients treated with clopidogrel.
abstract: BACKGROUND
  Despite clopidogrel has been widely applied to patients with ischemic stroke combined with aspirin, decreased metabolic activation of clopidogrel still occurs because of genetic variations in CYP2C19.
  
  
  METHODS
  Three hundred twenty-one patients completed a genetic test for CYP2C19 loss of function (LOF) alleles in hospital. Cox regression models were used to assess the relationship between CYP2C19 genotypes with the primary endpoint, which was a composite of nonfatal ischemic stroke, myocardial infarction, or vascular death. Functional outcome was measured by the modified Rankin Scale (mRS) at 3months, 6months and 12months intervals. Binary logistic regression was used to analyze the correlation between poor functional outcome and CYP2C19 LOF alleles.
  
  
  RESULTS
  The CYP2C19 LOF alleles were independently associated with the primary endpoint. There was no significant association between poor functional outcome and CYP2C19 LOF allele (*2 and *3) in overall patients. After the participants were stratified by stent treatment into two groups, the polymorphisms of CYP2C19 had significant impact on poor prognosis at 3months and 6months but not at 12months in patients without stent. No correlation was found in patients with stent.
  
  
  CONCLUSIONS
  The CYP2C19 LOF alleles may increase the recurrent risk of ischemic events. The polymorphisms of CYP2C19 may be predictors of poor functional outcome of patients without stent, and the effect may be weakened by time.
authors.affiliation: Department of Neurology, Jinling Hospital, Second Military Medical University, Nanjing, China; Department of Geriatric Neurology, Jinling Hospital, Medical School of Nanjing University, Nanjing, China.
authors.forename: Yingting
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Department of Neurology, Jinling Hospital, Southern Medical University, Nanjing, China.
authors.forename: Huan
authors.initials: H
authors.lastname: Cai
authors.affiliation: Department of Geriatric Neurology, Jinling Hospital, Medical School of Nanjing University, Nanjing, China.
authors.forename: Guoqing
authors.initials: G
authors.lastname: Zhou
authors.affiliation: Department of Neurology, Jinling Hospital, Second Military Medical University, Nanjing, China. Electronic address: zhizhongn@gmail.com.
authors.forename: Zhizhong
authors.initials: Z
authors.lastname: Zhang
authors.affiliation: Department of Neurology, Jinling Hospital, Second Military Medical University, Nanjing, China. Electronic address: xfliu2@vip.163.com.
authors.forename: Xinfeng
authors.initials: X
authors.lastname: Liu
mesh_terms: D000368:Aged; D002545:Brain Ischemia / Q000150:complications; D000077144:Clopidogrel; D065731:Cytochrome P-450 CYP2C19 / Q000235:genetics*; D005260:Female; D005500:Follow-Up Studies; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D010597:Pharmacogenetics; D010975:Platelet Aggregation Inhibitors / Q000627:therapeutic use*; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D016016:Proportional Hazards Models; D012189:Retrospective Studies; D020521:Stroke / Q000188:drug therapy* / Q000209:etiology / Q000235:genetics*; D013988:Ticlopidine / Q000031:analogs & derivatives* / Q000627:therapeutic use; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: D010975:Platelet Aggregation Inhibitors; D000077144:Clopidogrel; D065731:Cytochrome P-450 CYP2C19; D013988:Ticlopidine
keywords: CYP2C19; Clopidogrel; Functional outcome; Genetic variants; Ischemic stroke; Loss of function alleles