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Pharmacogenomic Genome-Wide Meta-Analysis of Blood Pressure Response to ß-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.
Afiliação
  • Gong Y; From the Department of Pharmacotherapy and Translational Research and Center for Pharmacogenomics (Y.G., C.W.M., T.Y.L., J.G.G., R.M.C.-D., J.A.J.), Department of Community Health and Family Medicine, College of Medicine (K.H., S.O.F.S., R.W.C., J.G.G.), and Division of Cardiovascular Medicine, Coll
  • Wang Z; From the Department of Pharmacotherapy and Translational Research and Center for Pharmacogenomics (Y.G., C.W.M., T.Y.L., J.G.G., R.M.C.-D., J.A.J.), Department of Community Health and Family Medicine, College of Medicine (K.H., S.O.F.S., R.W.C., J.G.G.), and Division of Cardiovascular Medicine, Coll
  • Beitelshees AL; From the Department of Pharmacotherapy and Translational Research and Center for Pharmacogenomics (Y.G., C.W.M., T.Y.L., J.G.G., R.M.C.-D., J.A.J.), Department of Community Health and Family Medicine, College of Medicine (K.H., S.O.F.S., R.W.C., J.G.G.), and Division of Cardiovascular Medicine, Coll
  • McDonough CW; From the Department of Pharmacotherapy and Translational Research and Center for Pharmacogenomics (Y.G., C.W.M., T.Y.L., J.G.G., R.M.C.-D., J.A.J.), Department of Community Health and Family Medicine, College of Medicine (K.H., S.O.F.S., R.W.C., J.G.G.), and Division of Cardiovascular Medicine, Coll
  • Langaee TY; From the Department of Pharmacotherapy and Translational Research and Center for Pharmacogenomics (Y.G., C.W.M., T.Y.L., J.G.G., R.M.C.-D., J.A.J.), Department of Community Health and Family Medicine, College of Medicine (K.H., S.O.F.S., R.W.C., J.G.G.), and Division of Cardiovascular Medicine, Coll
  • Hall K; From the Department of Pharmacotherapy and Translational Research and Center for Pharmacogenomics (Y.G., C.W.M., T.Y.L., J.G.G., R.M.C.-D., J.A.J.), Department of Community Health and Family Medicine, College of Medicine (K.H., S.O.F.S., R.W.C., J.G.G.), and Division of Cardiovascular Medicine, Coll
  • Schmidt SO; From the Department of Pharmacotherapy and Translational Research and Center for Pharmacogenomics (Y.G., C.W.M., T.Y.L., J.G.G., R.M.C.-D., J.A.J.), Department of Community Health and Family Medicine, College of Medicine (K.H., S.O.F.S., R.W.C., J.G.G.), and Division of Cardiovascular Medicine, Coll
  • Curry RW; From the Department of Pharmacotherapy and Translational Research and Center for Pharmacogenomics (Y.G., C.W.M., T.Y.L., J.G.G., R.M.C.-D., J.A.J.), Department of Community Health and Family Medicine, College of Medicine (K.H., S.O.F.S., R.W.C., J.G.G.), and Division of Cardiovascular Medicine, Coll
  • Gums JG; From the Department of Pharmacotherapy and Translational Research and Center for Pharmacogenomics (Y.G., C.W.M., T.Y.L., J.G.G., R.M.C.-D., J.A.J.), Department of Community Health and Family Medicine, College of Medicine (K.H., S.O.F.S., R.W.C., J.G.G.), and Division of Cardiovascular Medicine, Coll
  • Bailey KR; From the Department of Pharmacotherapy and Translational Research and Center for Pharmacogenomics (Y.G., C.W.M., T.Y.L., J.G.G., R.M.C.-D., J.A.J.), Department of Community Health and Family Medicine, College of Medicine (K.H., S.O.F.S., R.W.C., J.G.G.), and Division of Cardiovascular Medicine, Coll
  • Boerwinkle E; From the Department of Pharmacotherapy and Translational Research and Center for Pharmacogenomics (Y.G., C.W.M., T.Y.L., J.G.G., R.M.C.-D., J.A.J.), Department of Community Health and Family Medicine, College of Medicine (K.H., S.O.F.S., R.W.C., J.G.G.), and Division of Cardiovascular Medicine, Coll
  • Chapman AB; From the Department of Pharmacotherapy and Translational Research and Center for Pharmacogenomics (Y.G., C.W.M., T.Y.L., J.G.G., R.M.C.-D., J.A.J.), Department of Community Health and Family Medicine, College of Medicine (K.H., S.O.F.S., R.W.C., J.G.G.), and Division of Cardiovascular Medicine, Coll
  • Turner ST; From the Department of Pharmacotherapy and Translational Research and Center for Pharmacogenomics (Y.G., C.W.M., T.Y.L., J.G.G., R.M.C.-D., J.A.J.), Department of Community Health and Family Medicine, College of Medicine (K.H., S.O.F.S., R.W.C., J.G.G.), and Division of Cardiovascular Medicine, Coll
  • Cooper-DeHoff RM; From the Department of Pharmacotherapy and Translational Research and Center for Pharmacogenomics (Y.G., C.W.M., T.Y.L., J.G.G., R.M.C.-D., J.A.J.), Department of Community Health and Family Medicine, College of Medicine (K.H., S.O.F.S., R.W.C., J.G.G.), and Division of Cardiovascular Medicine, Coll
  • Johnson JA; From the Department of Pharmacotherapy and Translational Research and Center for Pharmacogenomics (Y.G., C.W.M., T.Y.L., J.G.G., R.M.C.-D., J.A.J.), Department of Community Health and Family Medicine, College of Medicine (K.H., S.O.F.S., R.W.C., J.G.G.), and Division of Cardiovascular Medicine, Coll
Hypertension ; 67(3): 556-63, 2016 Mar.
Article em En | MEDLINE | ID: mdl-26729753
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 ß-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), ß=-4.42 mm Hg per variant allele). Similarly, LRRC15 rs11313667 was validated for systolic BP response to ß-blocker therapy with 3-group meta-analysis P=7.2×10(-8) and ß=-3.65 mm Hg per variant allele. In this first pharmacogenomic genome-wide meta-analysis of BP response to ß-blockers in African Americans, we identified novel variants that may provide valuable information for personalized antihypertensive treatment in this group.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Farmacogenética / Negro ou Afro-Americano / Pressão Sanguínea / Antagonistas Adrenérgicos beta / Estudo de Associação Genômica Ampla / Hipertensão Tipo de estudo: Risk_factors_studies / Systematic_reviews Limite: Humans País/Região como assunto: America do norte Idioma: En Revista: Hypertension Ano de publicação: 2016 Tipo de documento: Article

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Farmacogenética / Negro ou Afro-Americano / Pressão Sanguínea / Antagonistas Adrenérgicos beta / Estudo de Associação Genômica Ampla / Hipertensão Tipo de estudo: Risk_factors_studies / Systematic_reviews Limite: Humans País/Região como assunto: America do norte Idioma: En Revista: Hypertension Ano de publicação: 2016 Tipo de documento: Article
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