title: Relationship between CYP2C19 loss-of-function polymorphism and platelet reactivities with clopidogrel treatment in Japanese patients undergoing coronary stent implantation.
abstract: BACKGROUND
  CYP2C19 loss-of-function genotype (*2 and/or *3 alleles) is related to low responsiveness to clopidogrel, which is a risk factor for ischemic cardiac events. The contribution of these genotypes to platelet reactivity in Japanese patients in a steady state receiving dual antiplatelet therapy after coronary stenting was evaluated.
  
  
  RESULTS
  A total of 155 Japanese patients were classified according to their CYP2C19 loss-of-function genotype. Platelet reactivity was assayed by plasma levels of soluble P-selectin and platelet-derived microparticles, light transmittance aggregometry induced by ADP (ADP-LTA), shear stress-induced platelet aggregometry, vasodilator-stimulated phosphoprotein phosphorylation (VASP) index and the VerifyNow-P2Y12 assay. Linear and logistic regression models were used to assess the associations between CYP2C19 loss-of-function genotype and high on-treatment platelet reactivity. In total, 62 patients (40.0%) were extensive metabolizers (EMs), 70 (45.2%) were intermediate metabolizers (IMs) and 23 (14.8%) were poor metabolizers (PMs). ADP-specific assays (ADP-LTA, the VASP index and VerifyNow-P2Y12) differed according to CYP2C19 genotype, with a significant gene-dose effect (PMs>IMs>EMs). CYP2C19 loss-of-function carrier status was associated with more frequent high platelet reactivity. CYP2C19 loss-of-function genotype alone could explain 12.2%, 14.3%, and 14.7% of the variability in the ADP-LTA, VASP and VerifyNow-P2Y12 assays, respectively.
  
  
  CONCLUSIONS
  CYP2C19 loss-of-function genotype is associated with more frequent high platelet reactivity, as assessed by ADP-specific platelet function tests, in Japanese patients.
authors.affiliation: Department of Cardiology, Mie University Faculty of Medicine, Tsu, Japan.
authors.forename: Tomoyuki
authors.initials: T
authors.lastname: Nakata
authors.forename: Masatoshi
authors.initials: M
authors.lastname: Miyahara
authors.forename: Kaname
authors.initials: K
authors.lastname: Nakatani
authors.forename: Hideo
authors.initials: H
authors.lastname: Wada
authors.forename: Takashi
authors.initials: T
authors.lastname: Tanigawa
authors.forename: Fumihiko
authors.initials: F
authors.lastname: Komada
authors.forename: Kozo
authors.initials: K
authors.lastname: Hoshino
authors.forename: Toshikazu
authors.initials: T
authors.lastname: Aoki
authors.forename: Yuki
authors.initials: Y
authors.lastname: Nishimura
authors.forename: Satoshi
authors.initials: S
authors.lastname: Tamaru
authors.forename: Masaaki
authors.initials: M
authors.lastname: Ito
authors.forename: Masakatsu
authors.initials: M
authors.lastname: Nishikawa
mesh_terms: D001189:Aryl Hydrocarbon Hydroxylases / Q000235:genetics* / Q000378:metabolism; D044466:Asian People; D015815:Cell Adhesion Molecules / Q000097:blood; D000077144:Clopidogrel; D003331:Coronary Vessels; D065731:Cytochrome P-450 CYP2C19; D006801:Humans; D007564:Japan; D008840:Microfilament Proteins / Q000097:blood; D017202:Myocardial Ischemia / Q000097:blood / Q000235:genetics* / Q000473:pathology / Q000503:physiopathology / Q000628:therapy*; D019007:P-Selectin / Q000097:blood; D010750:Phosphoproteins / Q000097:blood; D010974:Platelet Aggregation / Q000235:genetics*; D010975:Platelet Aggregation Inhibitors; D010979:Platelet Function Tests; D011110:Polymorphism, Genetic; D011446:Prospective Studies; D015607:Stents; D013988:Ticlopidine / Q000008:administration & dosage / Q000031:analogs & derivatives*; D000098662:Vasodilator-Stimulated Phosphoprotein
chemical_list: D015815:Cell Adhesion Molecules; D008840:Microfilament Proteins; D019007:P-Selectin; D010750:Phosphoproteins; D010975:Platelet Aggregation Inhibitors; D000098662:Vasodilator-Stimulated Phosphoprotein; D000077144:Clopidogrel; D001189:Aryl Hydrocarbon Hydroxylases; C045793:CYP2C19 protein, human; D065731:Cytochrome P-450 CYP2C19; D013988:Ticlopidine