PON1 Meta-Analysis Group listed in Appendix.
Influence of the paraoxonase-1 Q192R genetic variant on clopidogrel responsiveness and recurrent cardiovascular events: a systematic review and meta-analysis
Article first published online: 3 JUL 2012
© 2012 International Society on Thrombosis and Haemostasis
Journal of Thrombosis and Haemostasis
Volume 10, Issue 7, pages 1242–1251, July 2012
How to Cite
RENY, J.-L., COMBESCURE, C., DAALI, Y., FONTANA, P. and for the PON1 Meta-Analysis Group (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: 1242–1251. doi: 10.1111/j.1538-7836.2012.04756.x
- Issue published online: 3 JUL 2012
- Article first published online: 3 JUL 2012
- Accepted manuscript online: 21 APR 2012 09:15AM EST
- Received 6 March 2012, accepted 17 April 2012
- ischemic events;
- platelet function
Summary. 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.