title: No association of paraoxonase-1 Q192R genotypes with platelet response to clopidogrel and risk of stent thrombosis after coronary stenting.
abstract: OBJECTIVE
  In clopidogrel-treated patients undergoing coronary stenting, high on-treatment platelet reactivity was linked to a higher risk of stent thrombosis (ST). Platelet response to clopidogrel is significantly influenced by genetic factors. Recently published findings showed a highly significant impact of a common polymorphism (Q192R) within the paraoxonase-1 (PON1) gene on clopidogrel treatment efficacy but no influence of the CYP2C19*2 genetic variant as previously demonstrated. The aim of this study was to assess the impact of the PON1 Q192R genotype in parallel to that of CYP2C19*2 on the antiplatelet effect of clopidogrel and the risk of ST in clopidogrel-treated patients.
  
  
  RESULTS
  In 1524 patients undergoing percutaneous coronary intervention, ADP-induced platelet aggregation was assessed in relation to PON1 Q192R and CYP2C19*2 genotypes. The clinical impact of genetic variants was investigated by comparing genotype frequencies of both genetic variants in a registry of 127 cases with early ST vs. an early ST-free control cohort (n = 1439). For PON1 Q192R genotypes, platelet aggregation values were similar across all genotype groups (P = 0.65). For CYP2C19*2 genotypes, significantly higher aggregation values were found in CYP2C19 wt/*2 and *2/*2 patients when compared with wt/wt allele carriers (P < 0.0001). Comparing genotype frequencies between ST cases and controls, no differences were observed for PON1 Q192R genotype distributions (P = 0.23), whereas the genotype distribution differed for CYP2C19*2 genotypes (P = 0.019).
  
  
  CONCLUSIONS
  The PON1 Q192R genotype did not influence platelet response to clopidogrel or the risk of ST in clopidogrel-treated patients, whereas the CYP2C19*2 genotype impacted on both antiplatelet effect of clopidogrel and risk of coronary ST.
authors.affiliation: Deutsches Herzzentrum München and 1. Medizinische Klinik, Klinikum rechts der Isar, Technische Universität München, Lazarettstrasse 36, Munich, Germany.
authors.forename: Dirk
authors.initials: D
authors.lastname: Sibbing
authors.forename: Werner
authors.initials: W
authors.lastname: Koch
authors.forename: Steffen
authors.initials: S
authors.lastname: Massberg
authors.forename: Robert A
authors.initials: RA
authors.lastname: Byrne
authors.forename: Julinda
authors.initials: J
authors.lastname: Mehilli
authors.forename: Stefanie
authors.initials: S
authors.lastname: Schulz
authors.forename: Katharina
authors.initials: K
authors.lastname: Mayer
authors.forename: Isabell
authors.initials: I
authors.lastname: Bernlochner
authors.forename: Albert
authors.initials: A
authors.lastname: Schömig
authors.forename: Adnan
authors.initials: A
authors.lastname: Kastrati
mesh_terms: D000368:Aged; D015906:Angioplasty, Balloon, Coronary / Q000379:methods; D001189:Aryl Hydrocarbon Hydroxylases / Q000235:genetics*; D043303:Aryldialkylphosphatase / Q000235:genetics*; D001241:Aspirin / Q000627:therapeutic use; D000077144:Clopidogrel; D003327:Coronary Disease / Q000097:blood / Q000235:genetics / Q000628:therapy; D065731:Cytochrome P-450 CYP2C19; D005260:Female; D005787:Gene Frequency; D005838:Genotype; D006083:Graft Occlusion, Vascular / Q000235:genetics*; D006579:Heterozygote; D006720:Homozygote; D006801:Humans; D008297:Male; D008875:Middle Aged; D010974:Platelet Aggregation / Q000187:drug effects; D010975:Platelet Aggregation Inhibitors / Q000627:therapeutic use*; D011110:Polymorphism, Genetic / Q000235:genetics*; D011446:Prospective Studies; D015607:Stents; D013988:Ticlopidine / Q000031:analogs & derivatives* / Q000627:therapeutic use
chemical_list: D010975:Platelet Aggregation Inhibitors; D000077144:Clopidogrel; D001189:Aryl Hydrocarbon Hydroxylases; C045793:CYP2C19 protein, human; D065731:Cytochrome P-450 CYP2C19; D043303:Aryldialkylphosphatase; C468406:PON1 protein, human; D013988:Ticlopidine; D001241:Aspirin