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

Gong Y, Wang Z, Beitelshees AL, McDonough CW, Langaee TY, Hall K, Schmidt SO, Curry RW Jr, Gums JG, Bailey KR, Boerwinkle E, Chapman AB, Turner ST, Cooper-DeHoff RM, Johnson JA.
Hypertension. 2016 Mar;67(3):556-63.
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 beta-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<5x10(-8) and suggestive variants with P<5x10(-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=2.5x10(-8), beta=-4.42 mm Hg per variant allele). Similarly, LRRC15 rs11313667 was validated for systolic BP response to beta-blocker therapy with 3-group meta-analysis P=7.2x10(-8) and beta=-3.65 mm Hg per variant allele. In this first pharmacogenomic genome-wide meta-analysis of BP response to beta-blockers in African Americans, we identified novel variants that may provide valuable information for personalized antihypertensive treatment in this group.
Consortium data used in this publication
ENCODE TF ChIP, TF motifs, HaploReg, described in text
References