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Author Notes:

Corresponding author: E-mail: wrwikoff@ucdavis.edu (WRW); kaddu001@mc.duke.edu (RKD)

Conceived and designed the experiments: JAJ RFF RKD.

Performed the experiments: HZ YG SB EC OF WRW.

Contributed reagents/materials/analysis tools: RCD ALB ABC JAJ. Wrote the paper: WRW RFF YG RKD.

We thank Andrew Lane for helpful comments on the manuscript.

The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

Competing Interests: YG serves on the editorial board for PLOS ONE. This does not alter the authors’ adherence to all the PLOS ONE policies on sharing data and materials.

Subject:

Research Funding:

The metabolomics work was funded by NIGMS (National Institute of General Medical Sciences) grant RC2-GM092729 “Metabolomics Network for Drug Response Phenotype”.

The PEAR study is supported by a grant from the National Institutes of Health (Bethesda, MD), grant # U01 GM074492, funded as part of the Pharmacogenetics Research Network.

Additional support for this work includes: K23 grants HL091120 (ALB) and HL086558 (RCD); CTSA grants UL1-RR029890 (University of Florida), UL1-RR025008 (Emory University), and UL1-RR024150 (Mayo Clinic); and funds from the Mayo Foundation.

Keywords:

  • Science & Technology
  • Multidisciplinary Sciences
  • Science & Technology - Other Topics
  • MULTIDISCIPLINARY SCIENCES
  • GLOBAL BIOCHEMICAL APPROACH
  • ETHNIC-DIFFERENCES
  • DRUG RESPONSE
  • HYPERTENSION
  • METABOLOMICS
  • THERAPY
  • WOMEN
  • GENE
  • MEN
  • PHARMACOGENOMICS

Pharmacometabolomics Reveals Racial Differences in Response to Atenolol Treatment

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Journal Title:

PLoS ONE

Volume:

Volume 8, Number 3

Publisher:

, Pages e57639-e57639

Type of Work:

Article | Final Publisher PDF

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.

Copyright information:

© 2013 Wikoff et al.

This is an Open Access work distributed under the terms of the Creative Commons Attribution 4.0 International License (https://creativecommons.org/licenses/by/4.0/).
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