title: Genetic and non-genetic factors responsible for antiplatelet effects of clopidogrel in Japanese patients undergoing coronary stent implantation: an algorithm to predict on-clopidogrel platelet reactivity.
abstract: BACKGROUND
  Antiplatelet effects of clopidogrel appear to be affected by various factors including genetic polymorphism. So far, there has been little information about the response of clopidogrel in Asians, whose prevalence of a CYP2C19 loss-of-function (LOF) allele is high.
  
  
  RESULTS
  We investigated background and clinical factors affecting on-clopidogrel platelet reactivity in Japanese patients undergoing coronary stent implantation (n=114). In univariate analysis, antiplatelet effects of clopidogrel in a steady state were associated with not only CYP2C19 genotypes but also several factors including dyslipidemia. In addition, we developed an algorithm that can estimate P2Y12 Reaction Units (PRU) in a steady state by multiple regression analysis and evaluated the adequacy of the algorithm by the Akaike Information Criterion.
  
  
  CONCLUSIONS
  We revealed several factors influencing on-clopidogrel platelet reactivity in Japanese patients. We also succeeded in developing an algorithm that estimates PRU in a steady state, although it is uncertain whether the algorithm can be applied to other populations.
authors.affiliation: Department of Clinical Pharmacology, Graduate School of Pharmaceutical Sciences, Chiba University, Chiba, Japan; Division of Pharmacy, University Hospital, Chiba University School of Medicine, Chiba, Japan.
authors.forename: Go
authors.initials: G
authors.lastname: Miura
authors.affiliation: Department of Clinical Pharmacology, Graduate School of Pharmaceutical Sciences, Chiba University, Chiba, Japan; Division of Pharmacy, University Hospital, Chiba University School of Medicine, Chiba, Japan; Clinical Research Center, University Hospital, Chiba University School of Medicine, Chiba, Japan. Electronic address: ariyoshi@faculty.chiba-u.jp.
authors.forename: Noritaka
authors.initials: N
authors.lastname: Ariyoshi
authors.affiliation: Clinical Research Center, University Hospital, Chiba University School of Medicine, Chiba, Japan.
authors.forename: Yasunori
authors.initials: Y
authors.lastname: Sato
authors.affiliation: Division of Pharmacy, University Hospital, Chiba University School of Medicine, Chiba, Japan.
authors.forename: Hiroki
authors.initials: H
authors.lastname: Yamaguchi
authors.affiliation: Department of Cardiovascular Medicine, Chiba University Graduate School of Medicine, Chiba, Japan.
authors.forename: Yo
authors.initials: Y
authors.lastname: Iwata
authors.affiliation: Department of Cardiovascular Medicine, Chiba University Graduate School of Medicine, Chiba, Japan.
authors.forename: Yoshihide
authors.initials: Y
authors.lastname: Fujimoto
authors.affiliation: Department of Cardiovascular Medicine, Chiba University Graduate School of Medicine, Chiba, Japan.
authors.forename: Yoshio
authors.initials: Y
authors.lastname: Kobayashi
authors.affiliation: Department of Clinical Pharmacology, Graduate School of Pharmaceutical Sciences, Chiba University, Chiba, Japan; Division of Pharmacy, University Hospital, Chiba University School of Medicine, Chiba, Japan.
authors.forename: Itsuko
authors.initials: I
authors.lastname: Ishii
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000465:Algorithms; D044466:Asian People / Q000235:genetics; D001792:Blood Platelets / Q000166:cytology / Q000187:drug effects*; D000077144:Clopidogrel; D065731:Cytochrome P-450 CYP2C19 / Q000235:genetics; D005260:Female; D005838:Genotype; D006801:Humans; D016014:Linear Models; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D010597:Pharmacogenetics; D010974:Platelet Aggregation / Q000187:drug effects*; D010975:Platelet Aggregation Inhibitors / Q000494:pharmacology*; D010979:Platelet Function Tests; D058921:Purinergic P2Y Receptor Antagonists / Q000494:pharmacology*; D015607:Stents; D013988:Ticlopidine / Q000031:analogs & derivatives* / Q000494:pharmacology
chemical_list: D010975:Platelet Aggregation Inhibitors; D058921:Purinergic P2Y Receptor Antagonists; D000077144:Clopidogrel; D065731:Cytochrome P-450 CYP2C19; D013988:Ticlopidine
keywords: AIC; Algorithm; CYP2C19; Clopidgrel; Pharmacogenetics; VerifyNow