Dataset Information

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

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 ?-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), ?=-4.42 mm?Hg per variant allele). Similarly, LRRC15 rs11313667 was validated for systolic BP response to ?-blocker therapy with 3-group meta-analysis P=7.2×10(-8) and ?=-3.65 mm?Hg per variant allele. In this first pharmacogenomic genome-wide meta-analysis of BP response to ?-blockers in African Americans, we identified novel variants that may provide valuable information for personalized antihypertensive treatment in this group.

SUBMITTER: Gong Y

PROVIDER: S-EPMC4752391 | biostudies-literature | 2016 Mar

REPOSITORIES: biostudies-literature

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Publications

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

Gong Yan Y Wang Zhiying Z Beitelshees Amber L AL McDonough Caitrin W CW Langaee Taimour Y TY Hall Karen K Schmidt Siegfried O F SO Curry Robert W RW Gums John G JG Bailey Kent R KR Boerwinkle Eric E Chapman Arlene B AB Turner Stephen T ST Cooper-DeHoff Rhonda M RM Johnson Julie A JA

Hypertension (Dallas, Tex. : 1979) 20160104 3

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 wi ...[more]

PMID: 26729753

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Project description:BACKGROUND:African Americans (AA) are disproportionately affected by hypertension-related health disparities. Apolipoprotein L1 (APOL1) risk variants are associated with kidney disease in hypertensive AAs. OBJECTIVES:This study assessed the APOL1 risk alleles' association with blood pressure traits in AAs. METHODS:The discovery cohort included 5,204 AA participants from Mount Sinai's BioMe biobank. Replication cohorts included additional BioMe (n = 1,623), Vanderbilt BioVU (n = 1,809), and Northwestern NUgene (n = 567) AA biobank participants. Single nucleotide polymorphisms determining APOL1 G1 and G2 risk alleles were genotyped in BioMe and imputed in BioVU/NUgene participants. APOL1 risk alleles' association with blood pressure-related traits was tested in the discovery cohort, a meta-analysis of replication cohorts, and a combined meta-analysis under recessive and additive models after adjusting for age, sex, body mass index, and estimated glomerular filtration rate. RESULTS:There were 14% to 16% of APOL1 variant allele homozygotes (2 copies of G1/G2) across cohorts. APOL1 risk alleles were associated under an additive model with systolic blood pressure (SBP) and age at diagnosis of hypertension, which was 2 to 5 years younger in the APOL1 variant allele homozygotes (Cox proportional hazards analysis, p value for combined meta-analysis [pcom] = 1.9 × 10-5). APOL1 risk alleles were associated with overall SBP (pcom = 7.0 × 10-8) and diastolic blood pressure (pcom = 2.8 × 10-4). After adjustment for all covariates, those in the 20- to 29-year age range showed an increase in SBP of 0.94 ± 0.44 mm Hg (pcom = 0.01) per risk variant copy. APOL1-associated estimated glomerular filtration rate decline was observed starting a decade later in life in the 30- to 39-year age range. CONCLUSIONS:APOL1 risk alleles are associated with higher SBP and earlier hypertension diagnoses in young AAs; this relationship appears to follow an additive model.

Dataset Information

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

Publications

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

Similar Datasets

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