Paraoxonase 1 (PON1) Gene Variants Are Not Associated With Clopidogrel Response
Authors:
- 31 August 2011
- journal article
- research article
- Published by Wiley in Clinical Pharmacology & Therapeutics
- Vol. 90 (4) , 568-574
Abstract
A common functional variant in paraoxonase 1 (PON1), Q192R, was recently reported to be a major determinant of clopidogrel response. This variant was genotyped in 566 participants of the Amish Pharmacogenomics of Anti–Platelet Intervention (PAPI) study and in 227 percutaneous coronary intervention (PCI) patients. Serum paraoxonase activity was measured in a subset of 79 PAPI participants. PON1 Q192R was not associated with pre– or post–clopidogrel platelet aggregation in the PAPI study (P = 0.16 and P = 0.21, respectively) or the PCI cohort (P = 0.47 and P = 0.91, respectively). The Q192 allele was not associated with cardiovascular events (hazard ratio (HR) 0.46, 95% confidence interval (CI) 0.20–1.06; P = 0.07). No correlation was observed between paraoxonase activity and post–clopidogrel platelet aggregation (r2 < 0.01, P = 0.78). None of 49 additional PON1 variants evaluated was associated with post–clopidogrel platelet aggregation. These findings do not support a role for PON1 as a determinant of clopidogrel response. Clinical Pharmacology & Therapeutics (2011) 90 4, 568–574. doi:10.1038/clpt.2011.194Keywords
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