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

Research output: Article

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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 - júl. 2012

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clopidogrel
Aryldialkylphosphatase
Meta-Analysis

ASJC Scopus subject areas

  • Hematology

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

In: Journal of Thrombosis and Haemostasis, Vol. 10, No. 7, 07.2012, p. 1242-1251.

Research output: Article

Reny, JL, Combescure, C, Daali, Y, Fontana, P, Aradi, D, Delaney, J, Déry, JP, 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, vol. 10, no. 7, pp. 1242-1251. https://doi.org/10.1111/j.1538-7836.2012.04756.x
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. / Influence of the paraoxonase-1 Q192R genetic variant on clopidogrel responsiveness and recurrent cardiovascular events : A systematic review and meta-analysis. In: Journal of Thrombosis and Haemostasis. 2012 ; Vol. 10, No. 7. pp. 1242-1251.
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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. 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.",
keywords = "Clopidogrel, Ischemic events, Paraoxonase-1, Platelet function",
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T1 - Influence of the paraoxonase-1 Q192R genetic variant on clopidogrel responsiveness and recurrent cardiovascular events

T2 - A systematic review and meta-analysis

AU - Reny, J. L.

AU - Combescure, C.

AU - Daali, Y.

AU - Fontana, P.

AU - Aradi, D.

AU - Delaney, J.

AU - Déry, J. P.

AU - Gurbel, P.

AU - Lewis, J.

AU - Sibbing, D.

AU - Taubert, D.

AU - Trenk, D.

PY - 2012/7

Y1 - 2012/7

N2 - 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.

AB - 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.

KW - Clopidogrel

KW - Ischemic events

KW - Paraoxonase-1

KW - Platelet function

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