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Atenolol induced HDL-C change in the pharmacogenomic evaluation of antihypertensive responses (PEAR) study

Caitrin W McDonough1, Nancy K Gillis, Abdullah Alsultan

  • 1Department of Pharmacotherapy and Translational Research and Center for Pharmacogenomics, University of Florida, College of Pharmacy, Gainesville, Florida, United States of America.

Plos One
|October 12, 2013
PubMed

Insights

This study identified gene regions linked to high-density lipoprotein cholesterol (HDL-C) changes in hypertensive patients treated with atenolol. These findings suggest potential pharmacogenomic markers for predicting HDL-C response to atenolol across different racial groups.

Area of Science:

  • Pharmacogenomics
  • Cardiovascular Genetics
  • Hypertension Research

Background:

  • Identifying genetic markers can personalize hypertension treatment.
  • Atenolol's effect on high-density lipoprotein cholesterol (HDL-C) varies among individuals.
  • Pharmacogenomic Evaluation of Antihypertensive Responses (PEAR) study provided data on treatment responses.

Purpose of the Study:

  • To discover novel pharmacogenomic markers for HDL-C response to atenolol in hypertensive patients.
  • To evaluate genetic associations with atenolol-induced HDL-C changes across different racial groups.

Main Methods:

  • Genotyped 768 hypertensive participants from the PEAR study using Illumina HumanCVD Beadchip.
  • Focused on participants receiving atenolol monotherapy, analyzing 232 whites and 152 African Americans.
  • Utilized linear regression to assess associations between genetic variants and HDL-C changes, with Bonferroni correction applied.

Main Results:

  • No single nucleotide polymorphisms (SNPs) reached Bonferroni significance, but 13 regions showed consistent association across racial groups.
  • Seven regions, including GALNT2, FTO, ABCB1, LRP5, STARD3NL, ESR1, and LIPC, had prior links to HDL-C or lipid metabolism.
  • Specific examples include rs2144300 in GALNT2 (whites) and rs12595985 in FTO (African Americans), both showing cross-racial relevance. Baseline GALNT2 expression varied by rs2144300 genotype in whites.

Conclusions:

  • Multiple gene regions are associated with atenolol-induced HDL-C changes, with consistent findings across white and African American populations.
  • Several identified regions possess functional relevance or have prior associations with HDL-C and lipid pathways.
  • These findings highlight potential pharmacogenomic markers for predicting atenolol's impact on HDL-C levels.

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