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

19 Citations (Scopus)

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-8 and suggestive variants with P-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

Fingerprint

Pharmacogenetics
African Americans
Meta-Analysis
Genome
Atenolol
Blood Pressure
Metoprolol
Antihypertensive Agents
Alleles
Hypertension
Therapeutics
Hydrochlorothiazide
Genome-Wide Association Study
Ethnic Groups
Genotype

Keywords

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

ASJC Scopus subject areas

  • Internal Medicine

Cite this

Gong, Y., Wang, Z., Beitelshees, A. L., McDonough, C. W., Langaee, T. Y., Hall, K., ... 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

Pharmacogenomic Genome-Wide Meta-Analysis of Blood Pressure Response to β-Blockers in Hypertensive African Americans. / Gong, Yan; Wang, Zhiying; Beitelshees, Amber L.; McDonough, Caitrin W.; Langaee, Taimour Y.; Hall, Karen; Schmidt, Siegfried O F; Curry, Robert W.; Gums, John G.; Bailey, Kent R; Boerwinkle, Eric; Chapman, Arlene B.; Turner, Stephen T; Cooper-Dehoff, Rhonda M.; Johnson, Julie A.

In: Hypertension, Vol. 67, No. 3, 01.03.2016, p. 556-563.

Research output: Contribution to journalArticle

Gong, Y, Wang, Z, Beitelshees, AL, McDonough, CW, Langaee, TY, Hall, K, Schmidt, SOF, Curry, RW, Gums, JG, Bailey, KR, Boerwinkle, E, Chapman, AB, Turner, ST, Cooper-Dehoff, RM & Johnson, JA 2016, 'Pharmacogenomic Genome-Wide Meta-Analysis of Blood Pressure Response to β-Blockers in Hypertensive African Americans', Hypertension, vol. 67, no. 3, pp. 556-563. https://doi.org/10.1161/HYPERTENSIONAHA.115.06345
Gong, Yan ; Wang, Zhiying ; Beitelshees, Amber L. ; McDonough, Caitrin W. ; Langaee, Taimour Y. ; Hall, Karen ; Schmidt, Siegfried O F ; Curry, Robert W. ; Gums, John G. ; Bailey, Kent R ; Boerwinkle, Eric ; Chapman, Arlene B. ; Turner, Stephen T ; Cooper-Dehoff, Rhonda M. ; Johnson, Julie A. / Pharmacogenomic Genome-Wide Meta-Analysis of Blood Pressure Response to β-Blockers in Hypertensive African Americans. In: Hypertension. 2016 ; Vol. 67, No. 3. pp. 556-563.
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