The Correlation between Genetic Polymorphism of P2Y12, PON1, CYP2C19, CES-1 and PEAR-1 and Clinical Response to Dual Antiplatelet Treatment in Egyptian Patients with Acute Coronary Syndrome

Abstract

ABSTRACT Dual antiplatelet therapy (DAPT) with aspirin and Clopidogrel reduces the risk for recurrent cardiovascular events after acute coronary syndrome (ACS) and percutaneous coronary intervention. However, there is significant variation in response to DAPT that may be influenced by both genetic and non-genetic factors. The aim of the present study was to assess the effect of genetic polymorphisms in PON1, PEAR-1, P2Y12, CES1 and CYP2C19 along with clinical, demographic, and social factors, on variation in response to Clopidogrel plus aspirin therapy in Egyptians. This study included 230 Egyptian patients treated with Clopidogrel 75 mg/day and aspirin 81 mg/day for at least 12 months following their first ACS. It was found that CYP2C19*2 polymorphism was the only genetic predictor of major adverse cardiovascular events (MACE), defined as the occurrence of recurrent ACS, ischemic stroke, stent-related revascularization or death (OR 2.23, 95% CI: 1.15 – 4.33, p=0.01). Moreover, the use of proton pump inhibitor (PPI) (OR 4.77, 95% CI: 1.47 – 15.54, p=0.009) and diabetes (OR 1.83, 95% CI: 1.03 – 3.26, p=0.03) were associated with higher cardiovascular risk, while the use of statins was associated with lower risk (OR 0.43, 95% CI: 0.25 – 0.76, p=0.003). The contribution of these five genetic and non-genetic factors explained 19% of the variability in risk for MACE in Egyptians treated with Clopidogrel and aspirin. The previously mentioned results showed that CYP2C19*2 polymorphism, along with diabetes, and use of PPI and statins are important factors highly associated with the variability in clinical response to Clopidogrel plus aspirin following ACS in Egyptians.