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Pharmacometabolomics reveals racial differences in response to atenolol treatment.

Publication ,  Journal Article
Wikoff, WR; Frye, RF; Zhu, H; Gong, Y; Boyle, S; Churchill, E; Cooper-Dehoff, RM; Beitelshees, AL; Chapman, AB; Fiehn, O; Johnson, JA ...
Published in: PLoS One
2013

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.

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Published In

PLoS One

DOI

EISSN

1932-6203

Publication Date

2013

Volume

8

Issue

3

Start / End Page

e57639

Location

United States

Related Subject Headings

  • White People
  • Risk Factors
  • Polymorphism, Single Nucleotide
  • Pharmacogenetics
  • Middle Aged
  • Metabolomics
  • Metabolome
  • Metabolic Networks and Pathways
  • Male
  • Hypertension
 

Citation

APA
Chicago
ICMJE
MLA
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Wikoff, W. R., Frye, R. F., Zhu, H., Gong, Y., Boyle, S., Churchill, E., … Pharmacometabolomics Research Network, . (2013). Pharmacometabolomics reveals racial differences in response to atenolol treatment. PLoS One, 8(3), e57639. https://doi.org/10.1371/journal.pone.0057639
Wikoff, William R., Reginald F. Frye, Hongjie Zhu, Yan Gong, Stephen Boyle, Erik Churchill, Rhonda M. Cooper-Dehoff, et al. “Pharmacometabolomics reveals racial differences in response to atenolol treatment.PLoS One 8, no. 3 (2013): 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;8(3):e57639.
Wikoff, William R., et al. “Pharmacometabolomics reveals racial differences in response to atenolol treatment.PLoS One, vol. 8, no. 3, 2013, p. e57639. Pubmed, doi:10.1371/journal.pone.0057639.
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, Pharmacometabolomics Research Network. Pharmacometabolomics reveals racial differences in response to atenolol treatment. PLoS One. 2013;8(3):e57639.

Published In

PLoS One

DOI

EISSN

1932-6203

Publication Date

2013

Volume

8

Issue

3

Start / End Page

e57639

Location

United States

Related Subject Headings

  • White People
  • Risk Factors
  • Polymorphism, Single Nucleotide
  • Pharmacogenetics
  • Middle Aged
  • Metabolomics
  • Metabolome
  • Metabolic Networks and Pathways
  • Male
  • Hypertension