Pharmacometabolomics Reveals Racial Differences in Response to Atenolol Treatment

William R. Wikoff, Reginald F. Frye, Hongjie Zhu, Yan Gong, Stephen Boyle, Erik Churchill, Rhonda M. Cooper-Dehoff, Amber L. Beitelshees, Arlene B. Chapman, Oliver Fiehn, Julie A. Johnson, Rima Kaddurah-Daouk

Research output: Contribution to journalArticle

50 Citations (Scopus)

Abstract

Antihypertensive drugs are among the most commonly prescribed drugs for chronic disease worldwide. The response to antihypertensive drugs varies substantially between individuals and important factors such as race that contribute to this heterogeneity are poorly understood. In this study we use metabolomics, a global biochemical approach to investigate biochemical changes induced by the beta-adrenergic receptor blocker atenolol in Caucasians and African Americans. Plasma from individuals treated with atenolol was collected at baseline (untreated) and after a 9 week treatment period and analyzed using a GC-TOF metabolomics platform. The metabolomic signature of atenolol exposure included saturated (palmitic), monounsaturated (oleic, palmitoleic) and polyunsaturated (arachidonic, linoleic) free fatty acids, which decreased in Caucasians after treatment but were not different in African Americans (p<0.0005, q<0.03). Similarly, the ketone body 3-hydroxybutyrate was significantly decreased in Caucasians by 33% (p<0.0001, q<0.0001) but was unchanged in African Americans. The contribution of genetic variation in genes that encode lipases to the racial differences in atenolol-induced changes in fatty acids was examined. SNP rs9652472 in LIPC was found to be associated with the change in oleic acid in Caucasians (p<0.0005) but not African Americans, whereas the PLA2G4C SNP rs7250148 associated with oleic acid change in African Americans (p<0.0001) but not Caucasians. Together, these data indicate that atenolol-induced changes in the metabolome are dependent on race and genotype. This study represents a first step of a pharmacometabolomic approach to phenotype patients with hypertension and gain mechanistic insights into racial variability in changes that occur with atenolol treatment, which may influence response to the drug.

Original languageEnglish (US)
Article numbere57639
JournalPLoS One
Volume8
Issue number3
DOIs
StatePublished - Mar 11 2013

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Atenolol
African Americans
metabolomics
Metabolomics
antihypertensive agents
oleic acid
Oleic Acid
Antihypertensive Agents
Single Nucleotide Polymorphism
3-hydroxybutyric acid
Therapeutics
ketone bodies
metabolome
drugs
Ketone Bodies
Adrenergic beta-Antagonists
chronic diseases
3-Hydroxybutyric Acid
Metabolome
Receptors, Adrenergic, beta

ASJC Scopus subject areas

  • Agricultural and Biological Sciences(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

Cite this

Wikoff, W. R., Frye, R. F., Zhu, H., Gong, Y., Boyle, S., Churchill, E., ... Kaddurah-Daouk, R. (2013). Pharmacometabolomics Reveals Racial Differences in Response to Atenolol Treatment. PLoS One, 8(3), [e57639]. https://doi.org/10.1371/journal.pone.0057639

Pharmacometabolomics Reveals Racial Differences in Response to Atenolol Treatment. / Wikoff, William R.; Frye, Reginald F.; Zhu, Hongjie; Gong, Yan; Boyle, Stephen; Churchill, Erik; Cooper-Dehoff, Rhonda M.; Beitelshees, Amber L.; Chapman, Arlene B.; Fiehn, Oliver; Johnson, Julie A.; Kaddurah-Daouk, Rima.

In: PLoS One, Vol. 8, No. 3, e57639, 11.03.2013.

Research output: Contribution to journalArticle

Wikoff, WR, Frye, RF, Zhu, H, Gong, Y, Boyle, S, Churchill, E, Cooper-Dehoff, RM, Beitelshees, AL, Chapman, AB, Fiehn, O, Johnson, JA & Kaddurah-Daouk, R 2013, 'Pharmacometabolomics Reveals Racial Differences in Response to Atenolol Treatment', PLoS One, vol. 8, no. 3, e57639. https://doi.org/10.1371/journal.pone.0057639
Wikoff WR, Frye RF, Zhu H, Gong Y, Boyle S, Churchill E et al. Pharmacometabolomics Reveals Racial Differences in Response to Atenolol Treatment. PLoS One. 2013 Mar 11;8(3). e57639. https://doi.org/10.1371/journal.pone.0057639
Wikoff, William R. ; Frye, Reginald F. ; Zhu, Hongjie ; Gong, Yan ; Boyle, Stephen ; Churchill, Erik ; Cooper-Dehoff, Rhonda M. ; Beitelshees, Amber L. ; Chapman, Arlene B. ; Fiehn, Oliver ; Johnson, Julie A. ; Kaddurah-Daouk, Rima. / Pharmacometabolomics Reveals Racial Differences in Response to Atenolol Treatment. In: PLoS One. 2013 ; Vol. 8, No. 3.
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