title: Influence of the paraoxonase-1 Q192R genetic variant on clopidogrel responsiveness and recurrent cardiovascular events: a systematic review and meta-analysis.
abstract: BACKGROUND
  A poor biological response to clopidogrel is associated with an increased risk of major cardiovascular ischemic events (MACE). Paraoxonase 1 (PON1) enzyme activity is modulated by the PON1-Q192R variant (rs662) and was recently suggested to be strongly involved in clopidogrel bioactivation, but the influence of the PON1-Q192R variant on the risk of MACE in clopidogrel-treated patients is controversial.
  
  
  OBJECTIVE
  To determine whether the PON1-Q192R variant influences clopidogrel biological responsiveness and the risk of MACE in patients treated with clopidogrel.
  
  
  METHODS
  Systematic review and meta-analysis of studies of the association between the PON1-Q192R polymorphism and the biological response to clopidogrel and/or the risk of MACE during clopidogrel administration.
  
  
  RESULTS
  Seventeen studies were included. In the 12 studies of the biological response to clopidogrel (n = 5302 patients), there was no significant difference between 192QQ and 192QR + 192RR subjects, whatever the laboratory method used (global mean standardized difference = 0.10 [-0.06; 0.25], P = 0.22). Eleven studies assessed the risk of MACE, four using a case-control design (n = 2739 patients) and seven a prospective design (n = 5353 patients). Overall, MACE occurred in 19% of patients in case-control studies and in 6% of patients in prospective cohort studies, with no significant difference between 192QQ and 192QR + 192RR patients (OR = 1.28 [0.97; 1.68], P = 0.08). Similar results were obtained when study design was taken into account. Heterogeneity was mainly driven by one publication.
  
  
  CONCLUSIONS
  This meta-analysis suggests that the PON1-Q192R polymorphism has no major impact on the risk of MACE and does not alter the biological response to clopidogrel in clopidogrel-treated patients.
authors.affiliation: Division of General Internal Medicine, Faculty of MedicineGeneva University Hospital, Geneva, Switzerland.
authors.forename: J-L
authors.initials: JL
authors.lastname: Reny
authors.forename: C
authors.initials: C
authors.lastname: Combescure
authors.forename: Y
authors.initials: Y
authors.lastname: Daali
authors.forename: P
authors.initials: P
authors.lastname: Fontana
mesh_terms: D043303:Aryldialkylphosphatase / Q000235:genetics*; D002318:Cardiovascular Diseases / Q000188:drug therapy*; D000077144:Clopidogrel; D006801:Humans; D010975:Platelet Aggregation Inhibitors / Q000627:therapeutic use*; D012008:Recurrence; D013988:Ticlopidine / Q000031:analogs & derivatives* / Q000627:therapeutic use
chemical_list: D010975:Platelet Aggregation Inhibitors; D000077144:Clopidogrel; D043303:Aryldialkylphosphatase; C468406:PON1 protein, human; D013988:Ticlopidine