Skip NavigationSkip to Content
Return Return to Search Results

Genome-wide analysis of clopidogrel active metabolite levels identifies novel variants that influence antiplatelet response

  1. Author:
    Backman, Joshua D.
    O'Connell, Jeffrey R.
    Tanner, Keith
    Peer, Cody J.
    Figg, William D.
    Spencer, Shawn D.
    Mitchell, Braxton D.
    Shuldiner, Alan R.
    Yerges-Armstrong, Laura M.
    Horenstein, Richard B.
    Lewis, Joshua P.

  2. Author Address

    Univ Maryland, Sch Med, Div Endocrinol Diabet & Nutr, 660 W Redwood St,HH 498, Baltimore, MD 21201 USA.Univ Maryland, Sch Med, Program Personalized & Genom Med, 660 W Redwood St,HH 498, Baltimore, MD 21201 USA.Vet Adm Med Ctr, Ctr Geriatr Res Educ & Clin, Baltimore, MD 21218 USA.NCI, Clin Pharmacol Program, Bethesda, MD 20892 USA.NCI, Appl & Dev Res, SAIC Frederick Inc, Frederick, MD 21701 USA.
    1. Year: 2017
    2. Date: Apr
  2. Journal: PHARMACOGENETICS AND GENOMICS
  3. LIPPINCOTT WILLIAMS & WILKINS,
    1. 27
    2. 4
    3. Pages: 159-163
  5. Type of Article: Article
  6. ISSN: 1744-6872
  1. Abstract:

    Clopidogrel is one of the most commonly used therapeutics for the secondary prevention of cardiovascular events in patients with acute coronary syndromes. However, considerable interindividual variation in clopidogrel response has been documented, resulting in suboptimal therapy and an increased risk of recurrent events for some patients. In this investigation, we carried out the first genome-wide association study of circulating clopidogrel active metabolite levels in 513 healthy participants to directly measure clopidogrel pharmacokinetics. We observed that the CYP2C19 locus was the strongest genetic determinant of active metabolite formation (P=9.5x10(-15)). In addition, we identified novel genome-wide significant variants on chromosomes 3p25 (rs187941554, P=3.3x10(-11)) and 17q11 (rs80343429, P=1.3x10(-8)), as well as six additional loci that showed suggestive evidence of association (P <= 1.0x10(-6)). Four of these loci showed nominal associations with on-clopidogrel ADP-stimulated platelet aggregation (P0.05). Evaluation of clopidogrel active metabolite concentration may help identify novel genetic determinants of clopidogrel response, which has implications for the development of novel therapeutics and improved antiplatelet treatment for at-risk patients in the future. (C) 2017 Wolters Kluwer Health, Inc. All rights reserved.

    See More

  1. Keywords:

External Sources

  1. View Full Text
  2. DOI: 10.1097/FPC.0000000000000272
  3. PMID: 28207573
  4. PMCID: PMC5346037
  5. View record in Web of Science®
  6. WOS: 000398197800005

Library Notes

  1. Fiscal Year: FY2016-2017
NCI at Frederick

You are leaving a government website.

This external link provides additional information that is consistent with the intended purpose of this site. The government cannot attest to the accuracy of a non-federal site.

Linking to a non-federal site does not constitute an endorsement by this institution or any of its employees of the sponsors or the information and products presented on the site. You will be subject to the destination site's privacy policy when you follow the link.

ContinueCancel