Pharmacogenomic Genome-Wide Meta-Analysis of Blood Pressure Response to β-Blockers in Hypertensive African Americans

Yan Gong, Zhiying Wang, Amber L. Beitelshees, Caitrin W. McDonough, Taimour Y. Langaee, Karen Hall, Siegfried O.F. Schmidt, Robert W. Curry, John G. Gums, Kent R. Bailey, Eric Boerwinkle, Arlene B. Chapman, Stephen T. Turner, Rhonda M. Cooper-Dehoff, Julie A. Johnson

Research output: Contribution to journalArticle

22 Scopus citations

Abstract

African Americans suffer a higher prevalence of hypertension compared with other racial/ethnic groups. In this study, we performed a pharmacogenomic genome-wide association study of blood pressure (BP) response to β-blockers in African Americans with uncomplicated hypertension. Genome-wide meta-analysis was performed in 318 African American hypertensive participants in the 2 Pharmacogenomic Evaluation of Antihypertensive Responses studies: 150 treated with atenolol monotherapy and 168 treated with metoprolol monotherapy. The analysis adjusted for age, sex, baseline BP and principal components for ancestry. Genome-wide significant variants with P<5×10-8 and suggestive variants with P<5×10-7 were evaluated in an additional cohort of 141 African Americans treated with the addition of atenolol to hydrochlorothiazide treatment. The validated variants were then meta-analyzed in these 3 groups of African Americans. Two variants discovered in the monotherapy meta-analysis were validated in the add-on therapy. African American participants heterozygous for SLC25A31 rs201279313 deletion versus wild-type genotype had better diastolic BP response to atenolol monotherapy, metoprolol monotherapy, and atenolol add-on therapy: -9.3 versus -4.6, -9.6 versus -4.8, and -9.7 versus -6.4 mm Hg, respectively (3-group meta-analysis P=2.5×10-8, β=-4.42 mm Hg per variant allele). Similarly, LRRC15 rs11313667 was validated for systolic BP response to β-blocker therapy with 3-group meta-analysis P=7.2×10-8 and β=-3.65 mm Hg per variant allele. In this first pharmacogenomic genome-wide meta-analysis of BP response to β-blockers in African Americans, we identified novel variants that may provide valuable information for personalized antihypertensive treatment in this group.

Original languageEnglish (US)
Pages (from-to)556-563
Number of pages8
JournalHypertension
Volume67
Issue number3
DOIs
StatePublished - Mar 1 2016

Keywords

  • African Americans
  • GWAS
  • PEAR
  • blood pressure response
  • pharmacogenomics
  • β-blockers

ASJC Scopus subject areas

  • Internal Medicine

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  • Cite this

    Gong, Y., Wang, Z., Beitelshees, A. L., McDonough, C. W., Langaee, T. Y., Hall, K., Schmidt, S. O. F., Curry, R. W., Gums, J. G., Bailey, K. R., Boerwinkle, E., Chapman, A. B., Turner, S. T., Cooper-Dehoff, R. M., & Johnson, J. A. (2016). Pharmacogenomic Genome-Wide Meta-Analysis of Blood Pressure Response to β-Blockers in Hypertensive African Americans. Hypertension, 67(3), 556-563. https://doi.org/10.1161/HYPERTENSIONAHA.115.06345