title: CYP2C19*2 and other genetic variants affecting platelet response to clopidogrel in patients undergoing percutaneous coronary intervention.
abstract: BACKGROUND
  Information regarding any possible additional effect of genetic variants other than CYP2C19*2 on platelet reactivity in patients undergoing percutaneous coronary intervention (PCI), while on dual antiplatelet therapy, is sparse.
  
  
  METHODS
  Genotyping for CYP2C19*2, CYP2C19*17, CYP2C9*3, CYP2B6*5, ABCB1 and P2RY12 (c.-217+2739T>C) variants was performed in 146 consecutive PCI patients receiving clopidogrel. Platelet reactivity was assessed by the Verify Now P2Y12 point-of-care assay and high on-treatment platelet reactivity (HTPR) was defined as a Platelet Reactivity Unit (PRU)≥235.
  
  
  RESULTS
  We identified 65(44.5%) patients with HTPR and 38(26%) carriers of at least one CYP2C19*2 allele, which had higher platelet reactivity compared to non-carriers [least square (LS) mean difference 44.5, 95%CI 15.8-77.3, p=0.003]. In the entire study population, the presence of at least one CYP2C19*2 or P2RY12 allelic variant was independently associated with HTPR (OR=3.02, 95%CI 1.16-7.86, p=0.023 and OR=3.11, 95%CI 1.03-9.39, p=0.05 respectively). In CYP2C19*2 non-carriers, carriers of at least one CYP2B6*5 allelic variant had higher platelet reactivity compared to the remainders (LS mean difference 35.6, 95%CI 3.7-67.6, p=0.03) and the presence of at least one CYP2B6*5 or P2RY12 allelic variant was independently associated with HTPR (OR=3.26, 95%CI 1.08-9.86, p=0.04 and OR=4.27, 95%CI 1.11-16.4, p=0.04 respectively).
  
  
  CONCLUSIONS
  Apart from the CYP2C19*2, other genetic variants involved in clopidogrel metabolism and action like CYP2B6*5 and P2RY12 seem to have an important association with HTPR.
authors.affiliation: Cardiology Department, University Hospital of Patras, Greece. gksup@yahoo.gr
authors.forename: George
authors.initials: G
authors.lastname: Kassimis
authors.forename: Periklis
authors.initials: P
authors.lastname: Davlouros
authors.forename: Ioanna
authors.initials: I
authors.lastname: Xanthopoulou
authors.forename: Eleana F
authors.initials: EF
authors.lastname: Stavrou
authors.forename: Aglaia
authors.initials: A
authors.lastname: Athanassiadou
authors.forename: Dimitrios
authors.initials: D
authors.lastname: Alexopoulos
mesh_terms: D000077144:Clopidogrel; D015897:Comorbidity; D003324:Coronary Artery Disease / Q000097:blood / Q000453:epidemiology / Q000601:surgery*; D016207:Cytokines / Q000235:genetics; D005260:Female; D020022:Genetic Predisposition to Disease / Q000453:epidemiology / Q000235:genetics; D006115:Greece / Q000453:epidemiology; D006801:Humans; D008297:Male; D015539:Platelet Activation / Q000187:drug effects* / Q000235:genetics*; D010975:Platelet Aggregation Inhibitors / Q000627:therapeutic use; D015995:Prevalence; D015607:Stents / Q000706:statistics & numerical data; D013927:Thrombosis / Q000453:epidemiology / Q000235:genetics* / Q000517:prevention & control*; D013988:Ticlopidine / Q000031:analogs & derivatives* / Q000627:therapeutic use; D016896:Treatment Outcome
chemical_list: D016207:Cytokines; D010975:Platelet Aggregation Inhibitors; D000077144:Clopidogrel; D013988:Ticlopidine