title: Paraoxonase 1 (PON1) gene variants are not associated with clopidogrel response.
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 (r(2) < 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.
authors: Division of Endocrinology, Diabetes and Nutrition, University of Maryland School of Medicine, Baltimore, Maryland, USA.
authors: J P
authors: JP
authors: Lewis
authors: A S
authors: AS
authors: Fisch
authors: K
authors: K
authors: Ryan
authors: J R
authors: JR
authors: O'Connell
authors: Q
authors: Q
authors: Gibson
authors: B D
authors: BD
authors: Mitchell
authors: H
authors: H
authors: Shen
authors: K
authors: K
authors: Tanner
authors: R B
authors: RB
authors: Horenstein
authors: R
authors: R
authors: Pakzy
authors: U S
authors: US
authors: Tantry
authors: K P
authors: KP
authors: Bliden
authors: P A
authors: PA
authors: Gurbel
authors: A R
authors: AR
authors: Shuldiner
mesh_terms: D000328:Adult; D000368:Aged; D043303:Aryldialkylphosphatase / Q000235:genetics*; D002318:Cardiovascular Diseases / Q000188:drug therapy / Q000235:genetics* / Q000401:mortality*; D000077144:Clopidogrel; D015331:Cohort Studies; D005260:Female; D005500:Follow-Up Studies; D056726:Genetic Association Studies / Q000379:methods*; D014644:Genetic Variation / Q000235:genetics*; D006801:Humans; D008297:Male; D008875:Middle Aged; D015996:Survival Rate / Q000639:trends; D013988:Ticlopidine / Q000031:analogs & derivatives* / Q000627:therapeutic use; D016896:Treatment Outcome
chemical_list: D000077144:Clopidogrel; D043303:Aryldialkylphosphatase; C468406:PON1 protein, human; D013988:Ticlopidine