About this item:

201 Views | 163 Downloads

Author Notes:

Correspondence: E-mail: Johnson@cop.ufl.edu

Conceived and designed the experiments: JAJ RMCD STT JGG ABC YG TYL CWM.

Performed the experiments: CWM NKG AA SWC MKS JEL MHAS TWB NMER ACCS.

Analyzed the data: CWM NKG AA SWC MKS JEL MHAS TWB NMER ACCS.

Contributed reagents/materials/analysis tools: JAJ RMCD STT JGG ABC.

Wrote the manuscript: CWM NKG AA SWC MKS JEL MHAS TWB TYL RMCD YG JAJ.

We acknowledge and thank the participants in the PEAR study.

We also acknowledge and thank the PEAR support staff, and study physicians: Drs. George Baramidze, R. Whit Curry, Karen Hall, Frederic Rabari-Oskoui, Dan Rubin, Siegfried Schmidt, and Michel Diab.

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

The authors have declared that no competing interests exist.

Subjects:

Research Funding:

PEAR was supported by the National Institute of Health Pharmacogenetics Research Network grant U01-GM074492 and the National Center for Advancing Translational Sciences under the award number UL1 TR000064 (University of Florida); UL1 TR000454 (Emory University) and UL1 TR000135 (Mayo Clinic).

PEAR efforts at the Mayo Clinic were also supported by funds from the Mayo Foundation. http://www.nih.gov/http://www.mayoclinic.com/.

Keywords:

  • Science & Technology
  • Multidisciplinary Sciences
  • Science & Technology - Other Topics
  • MULTIDISCIPLINARY SCIENCES
  • HIGH-DENSITY-LIPOPROTEIN
  • GENE-CENTRIC METAANALYSIS
  • WHOLE-GENOME ASSOCIATION
  • WIDE ASSOCIATION
  • STATIN THERAPY
  • CHOLESTEROL
  • LOCI
  • POPULATION
  • RISK
  • VISUALIZATION
  • African-American people
  • Genome-wide association studies
  • Alleles
  • Cholesterol
  • Gene expression
  • Hypertension
  • Variant genotypes
  • Lipid metabolism

Atenolol Induced HDL-C Change in the Pharmacogenomic Evaluation of Antihypertensive Responses (PEAR) Study

Show all authors Show less authors

Journal Title:

PLoS ONE

Volume:

Volume 8, Number 10

Publisher:

, Pages e76984-e76984

Type of Work:

Article | Final Publisher PDF

Abstract:

We sought to identify novel pharmacogenomic markers for HDL-C response to atenolol in participants with mild to moderate hypertension. We genotyped 768 hypertensive participants from the Pharmacogenomic Evaluation of Antihypertensive Responses (PEAR) study on the Illumina HumanCVD Beadchip. During PEAR, participants were randomized to receive atenolol or hydrochlorothiazide. Blood pressure and cholesterol levels were evaluated at baseline and after treatment. This study focused on participants treated with atenolol monotherapy. Association with atenolol induced HDL-C change was evaluated in 232 whites and 152 African Americans using linear regression. No SNPs achieved a Bonferroni corrected P-value. However, we identified 13 regions with consistent association across whites and African Americans. The most interesting of these regions were seven with prior associations with HDL-C, other metabolic traits, or functional implications in the lipid pathway: GALNT2, FTO, ABCB1, LRP5, STARD3NL, ESR1, and LIPC. Examples are rs2144300 in GALNT2 in whites (P=2.29x10 -4 , β=-1.85 mg/dL) and rs12595985 in FTO in African Americans (P=2.90x10 -4 , β=4.52 mg/dL), both with consistent regional association (P < 0.05) in the other race group. Additionally, baseline GALNT2 expression differed by rs2144300 genotype in whites (P=0.0279). In conclusion, we identified multiple gene regions associated with atenolol induced HDL-C change that were consistent across race groups, several with functional implications or prior associations with HDL-C.

Copyright information:

© 2013 McDonough 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/).
Export to EndNote