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Paraoxonase–1 (PON1) Q192R polymorphism was recently suggested to determine per se clopidogrel response on major cardiovascular events (MACEs). We assessed the impact of PON1, CYP2C19, and ABCB1 polymorphisms on MACE in clopidogrel–treated acute myocardial infarction (AMI) patients (N = 2,210), including those undergoing percutaneous coronary intervention (PCI) (n = 1,538). PON1 polymorphism was not associated with increased risk of in–hospital death and MACEs at 1 year (adjusted hazard ratio (HR) 1.03, 95% confidence interval (CI) 0.66–1.61 and adjusted HR 0.77, 95% CI 0.42–1.41 for QQ versus RR in all and PCI patients, respectively). The presence of two CYP2C19 loss–of–function (LOF) alleles was associated with the risk of in–hospital death and MACEs at 1 year in the overall population (adjusted odds ratio (OR) 3.67, 95% CI 1.05–12.80 and adjusted HR 1.96, 95% CI 1.08–3.54 …