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Clopidogrel’s responsiveness may be affected by the paraoxonase-1 (PON1) enzyme encoded by the  Q192R PON1  genetic variant. We aimed to determine the aggregated risk of MACEs associated with carrying Q192R  PON1  genetic variant in patients taking clopidogrel. Different databases were searched systematically for eligible studies, and risk ratio (RR) was measured using RevMan software where  P  &lt;0.05 was set statistically significant. Nineteen studies were included consisting of 17,815 patients. It was found that patients carrying either homozygous or a combination of heterozygous and homozygous variants were not significantly associated with increased risk of MACEs compared to the non-carriers ( QQ  vs.  RR : RR=0.99, 95% CI 0.69–1.42,  P =0.96;  QQ+QR  vs  RR ; RR=1.05, 95% CI 0.82–1.35,  P =0.70). The risk of MACEs was also not significantly different in other genetic model ( QQ  vs  QR+RR ) (RR=1.09, 95% CI 0.93–1.27,  P =0.30). Further, bleeding events were not significantly different in different genetic models ( QQ  vs  RR ; RR=1.13, 95% CI 0.58–2.21,  P =0.71;  QQ+QR  vs  RR ; RR=1.09, 95% CI 0.66–1.81,  P =0.73;  QQ  vs  QR+RR ; RR=1.08, 95% CI 0.76–1.55,  P =0.66). The results suggest that the  Q192R PON1  genetic polymorphism has no significant impact on the risk of MACEs or bleeding events in patients treated with clopidogrel.

expert opinion on drug safety

Association between  Q192R PON1  genetic polymorphism and major adverse cardiovascular events in patients treated with clopidogrel: an updated meta-analysis