Paraoxonase 1 (PON1) gene variants are not associated with clopidogrel response

J. P. Lewis, A. S. Fisch, K. Ryan, J. R. O'Connell, Q. Gibson, B. D. Mitchell, H. Shen, K. Tanner, R. B. Horenstein, R. Pakzy, U. S. Tantry, K. P. Bliden, P. A. Gurbel, A. R. Shuldiner

Research output: Contribution to journalReview articlepeer-review

70 Scopus citations


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.

Original languageEnglish (US)
Pages (from-to)568-574
Number of pages7
JournalClinical pharmacology and therapeutics
Issue number4
StatePublished - Oct 2011
Externally publishedYes

ASJC Scopus subject areas

  • Pharmacology
  • Pharmacology (medical)


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