Influence of the paraoxonase-1 Q192R genetic variant on clopidogrel responsiveness and recurrent cardiovascular events: A systematic review and meta-analysis

J. L. Reny, C. Combescure, Y. Daali, P. Fontana, D. Aradi, J. Delaney, J. P. Déry, P. Gurbel, J. Lewis, D. Sibbing, D. Taubert, D. Trenk

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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. Objectives: 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.

Original languageEnglish
Pages (from-to)1242-1251
Number of pages10
JournalJournal of Thrombosis and Haemostasis
Volume10
Issue number7
DOIs
Publication statusPublished - Jul 1 2012

Keywords

  • Clopidogrel
  • Ischemic events
  • Paraoxonase-1
  • Platelet function

ASJC Scopus subject areas

  • Hematology

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    Reny, J. L., Combescure, C., Daali, Y., Fontana, P., Aradi, D., Delaney, J., Déry, J. P., Gurbel, P., Lewis, J., Sibbing, D., Taubert, D., & Trenk, D. (2012). Influence of the paraoxonase-1 Q192R genetic variant on clopidogrel responsiveness and recurrent cardiovascular events: A systematic review and meta-analysis. Journal of Thrombosis and Haemostasis, 10(7), 1242-1251. https://doi.org/10.1111/j.1538-7836.2012.04756.x