title: CYP2C19 polymorphisms and antiplatelet effects of clopidogrel in acute ischemic stroke in China.
abstract: OBJECTIVE
  Little research regarding genotypes and clopidogrel response related to acute ischemic stroke has been published. This study was conducted to investigate whether the polymorphisms of receptors or enzymes involved in the metabolic process of clopidogrel affect clopidogrel response and prognosis related to acute stroke.
  
  
  METHODS
  A total of 259 patients with acute ischemic stroke were enrolled in this study; all received follow-up evaluations 3 and 6 months after clopidogrel treatment. CYP2C19, CYP3A4, and P2Y12 were screened. The adenosine diphosphate-induced platelet aggregation test, the National Institutes of Health Stroke Scale (NIHSS), and the modified Rankin Scale (mRS) were used, and blood vascular events were evaluated.
  
  
  RESULTS
  The difference before and after clopidogrel treatment on adenosine diphosphate-induced platelet aggregation was significantly smaller in patients carrying 1 or 2 CYP2C19 loss-of-function alleles (*2, *3) compared with patients carrying none. Patients with none had better outcomes than patients with CYP2C19 loss-of-function alleles, as demonstrated by NIHSS and mRS scores at 3 and 6 months after treatment. Regression analysis showed that CYP2C19 was an independent predictor of clopidogrel resistance.
  
  
  CONCLUSIONS
  CYP2C19 genotypes had significant impact on clopidogrel response and prognosis of patients with stroke. Clinical Trial Registration Information- URL: http://www.chictr.org/. Unique Identifier: ChiCTR-OCH-12002681.
authors: Department of Neurology, Drum Tower Hospital of Nanjing Medical University, 321 ZhongShan Rd, Nanjing City, Jiangsu Province, 210008, PR China.
authors: Dong-mei
authors: DM
authors: Jia
authors: Zhi-bin
authors: ZB
authors: Chen
authors: Mei-juan
authors: MJ
authors: Zhang
authors: Wen-jie
authors: WJ
authors: Yang
authors: Jia-li
authors: JL
authors: Jin
authors: Yong-quan
authors: YQ
authors: Xia
authors: Chun-lei
authors: CL
authors: Zhang
authors: Yuan
authors: Y
authors: Shao
authors: Cong
authors: C
authors: Chen
authors: Yun
authors: Y
authors: Xu
mesh_terms: D000368:Aged; D000483:Alleles; D001189:Aryl Hydrocarbon Hydroxylases / Q000235:genetics*; D044466:Asian People / Q000208:ethnology / Q000235:genetics*; D016022:Case-Control Studies; D002681:China / Q000453:epidemiology; D000077144:Clopidogrel; D065731:Cytochrome P-450 CYP2C19; D004351:Drug Resistance / Q000235:genetics; D005260:Female; D005500:Follow-Up Studies; D005820:Genetic Testing; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D010597:Pharmacogenetics; D010975:Platelet Aggregation Inhibitors / Q000627:therapeutic use*; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D011379:Prognosis; D020521:Stroke / Q000188:drug therapy* / Q000208:ethnology / Q000235:genetics*; D013988:Ticlopidine / Q000031:analogs & derivatives* / Q000627:therapeutic use; D016896:Treatment Outcome
chemical_list: D010975:Platelet Aggregation Inhibitors; D000077144:Clopidogrel; D001189:Aryl Hydrocarbon Hydroxylases; C045793:CYP2C19 protein, human; D065731:Cytochrome P-450 CYP2C19; D013988:Ticlopidine
keywords: CYP2C19 genotype; clopidogrel resistance; ischemic stroke; stroke outcome