title: Influence of CYP2C19 loss-of-function variants on the metabolism of clopidogrel in patients from north-western China.
abstract: OBJECTIVE
  Variation of the cytochrome P450 2C19 gene coding for the CYP2C19 enzyme has been reported to be associated with clopidogrel response variability. The activity of the CYP2C19 enzyme is genetically influenced by polymorphisms of its gene.
  
  
  METHODS
  This study was conducted to assess the impact of CYP2C19 polymorphism on the clopidogrel metabolism, indirectly selecting the plasma concentration ratios of clopidogrel to its inactive metabolite SR26334 as an evaluation index. Genotyping and plasma concentration results of 366 patients on clopidogrel maintenance therapy (75 mg daily dose) were analysed in this study. CYP2C19 genotypes were determined by PCR-restriction fragment length polymorphism method.
  
  
  CONCLUSIONS
  As for CYP2C19, patients were classified into three metabolism genotype groups: EM (44·3%), IM (43·4%) and PM (12·3%). The mean plasma concentration ratio of clopidogrel to its inactive metabolite SR26334 for the entire sample was 0·507. The plasma concentration ratios of the 3 metabolism groups were significantly different (P < 0·001). The lowest plasma concentration ratio value was observed for PM patients.
  
  
  CONCLUSIONS
  Polymorphism of CYP2C19 was significantly associated with plasma concentration ratios of clopidogrel to its inactive metabolite SR26334. Clopidogrel metabolism was regulated by CYP2C19. The *2 and *3 allele carriage were independently associated with the antiplatelet effect of chronic clopidogrel therapy.
authors: School of Pharmacology, Health Science Center, Xi'an Jiaotong University, Xi'an, China.
authors: R
authors: R
authors: Lin
authors: L
authors: L
authors: Zhang
authors: P
authors: P
authors: Zhang
authors: L
authors: L
authors: Zhou
authors: T
authors: T
authors: Liu
authors: Y
authors: Y
authors: Li
authors: W
authors: W
authors: Zhang
authors: W
authors: W
authors: Wang
authors: J
authors: J
authors: Zhang
mesh_terms: D000368:Aged; D044466:Asian People / Q000235:genetics; D002681:China; D000077144:Clopidogrel; D065731:Cytochrome P-450 CYP2C19 / Q000235:genetics* / Q000378:metabolism; D005260:Female; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D010975:Platelet Aggregation Inhibitors / Q000493:pharmacokinetics*; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic; D012150:Polymorphism, Restriction Fragment Length; D013988:Ticlopidine / Q000031:analogs & derivatives* / Q000097:blood / Q000493:pharmacokinetics
chemical_list: D010975:Platelet Aggregation Inhibitors; C521473:SR26334; D000077144:Clopidogrel; D065731:Cytochrome P-450 CYP2C19; D013988:Ticlopidine
keywords: CYP2C19; Clopidogrel; HPLC-MS/MS; plasma concentration ratio; polymorphism