Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Correspondence
  • Published:

Paraoxonase-1 and clopidogrel efficacy

Nature Medicine volume 17, pages 1041–1042 (2011)Cite this article

Subjects

To the Editor:

The incidence of stent thrombosis is decreasing steadily, in part as a result of the combined treatment of patients with clopidogrel and aspirin. In a recent publication in Nature Medicine, Bouman et al.1 demonstrated in vitro that oxidized clopidogrel is converted to the active thiol metabolite in a reaction catalyzed by PON1 (aryldialkylphosphatase, EC 3.1.8.1). Their results are plausible, as PON1 is known to catalyze the hydrolysis of thiolactones (as is oxo-clopidogrel), albeit at low rates2. They concluded that PON1 is a major determinant of clopidogrel efficacy. This is an important point, because it may imply that clopidogrel effectiveness depends on PON1 status. However, several aspects of the experimental procedures and data concern us and, in our opinion, merit further investigation.

This is a preview of subscription content, access via your institution

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

References

  1. Bouman, H.J. et al. Nat. Med. 17, 110–116 (2011).

    Article  CAS  Google Scholar 

  2. Jakubowski, H. J. Biol. Chem. 275, 3957–3962 (2000).

    Article  CAS  PubMed  Google Scholar 

  3. Erdös, E.G. & Boggs, L.E. Nature 190, 716–717 (1961).

    Article  PubMed  Google Scholar 

  4. Harel, M. Nat. Struct. Mol. Biol. 11, 412–419 (2004).

    Article  CAS  PubMed  Google Scholar 

  5. Mackness, M.I. & Walker, C.H. Biochem. Pharmacol. 30, 903–906 (1981).

    Article  CAS  PubMed  Google Scholar 

  6. Blatter Garin, M.-C. et al. Biochem. J. 304, 549–554 (1994).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. Pavković, E. et al. Chem. Biol. Interact. 87, 179–182 (1993).

    Article  PubMed  Google Scholar 

  8. Connelly, P.W. et al. Biochim. Biophys. Acta 1811, 39–45 (2011).

    Article  CAS  PubMed  Google Scholar 

  9. Ortigoza-Ferado, J. et al. Am. J. Hum. Genet. 36, 295–305 (1984).

    CAS  PubMed  PubMed Central  Google Scholar 

  10. Draganov, D.I. et al. J. Lipid Res. 46, 1239–1247 (2005).

    Article  CAS  PubMed  Google Scholar 

  11. Gaidukov, L. et al. BMC Clin. Pharmacol. 9, 18 (2009).

    Article  PubMed  PubMed Central  Google Scholar 

  12. Camps, J. et al. Crit. Rev. Clin. Lab. Sci. 46, 83–106 (2009).

    Article  CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Centre de Recerca Biomèdica, Institut d'Investigació Sanitària Pere Virgili, Universitat Rovira i Virgili, C. Sant Joan, Reus, Spain

    Jordi Camps, Jorge Joven, Bharti Mackness & Michael Mackness

  2. Department of Biological Chemistry, Weizmann Institute of Science, Rehovot, Israel

    Dan Tawfik

  3. WIL Research Laboratories, Ashland, Ohio, USA

    Dragomir Draganov

  4. Department of Environmental and Occupational Health Sciences, University of Washington, Seattle, Washington, USA

    Lucio G Costa

  5. Department of Internal Medicine, University of Debrecen, Hungary

    György Paragh & Ildikó Seres

  6. Institute of Pharmacology, University Medical Center, Meinz, Obere Zahlbacher, Meinz, Germany

    Sven Horke

  7. Department of Internal Medicine, University of Geneva, Switzerland

    Richard James

  8. Department of Toxicology, University of Granada, Granada, Spain

    Antonio Hernández

  9. Division of Cardiology, University of California–Los Angeles, Los Angeles, California, USA

    Srinivasa Reddy, Diana Shih & Mohamed Navab

  10. Département de Toxicologie, Centre de Recherches du Service de Santé des Armées, La Tronche Cedex, France

    Daniel Rochu

  11. The Lipid Research Laboratory, Technion Faculty of Medicine, Rambam Medical Center, Haifa, Israel

    Michael Aviram

Authors
  1. Jordi Camps
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Jorge Joven
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Bharti Mackness
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Michael Mackness
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Dan Tawfik
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Dragomir Draganov
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Lucio G Costa
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. György Paragh
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Ildikó Seres
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Sven Horke
    View author publications

    You can also search for this author in PubMed Google Scholar

  11. Richard James
    View author publications

    You can also search for this author in PubMed Google Scholar

  12. Antonio Hernández
    View author publications

    You can also search for this author in PubMed Google Scholar

  13. Srinivasa Reddy
    View author publications

    You can also search for this author in PubMed Google Scholar

  14. Diana Shih
    View author publications

    You can also search for this author in PubMed Google Scholar

  15. Mohamed Navab
    View author publications

    You can also search for this author in PubMed Google Scholar

  16. Daniel Rochu
    View author publications

    You can also search for this author in PubMed Google Scholar

  17. Michael Aviram
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Jordi Camps.

Ethics declarations

Competing interests

The authors declare no competing financial interests.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Camps, J., Joven, J., Mackness, B. et al. Paraoxonase-1 and clopidogrel efficacy. Nat Med 17, 1041–1042 (2011). https://doi.org/10.1038/nm.2386

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/nm.2386

This article is cited by

Search

Advanced search

Quick links

Nature Briefing: Translational Research

Sign up for the Nature Briefing: Translational Research newsletter — top stories in biotechnology, drug discovery and pharma.

Get what matters in translational research, free to your inbox weekly. Sign up for Nature Briefing: Translational Research