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Genomic Association Analysis Reveals Variants Associated With Blood Pressure Response to Beta‐Blockers in European Americans
European Americans (EA) have a better antihypertensive response to β‐blockers when compared with African Americans, albeit with some variability. We undertook a genomewide association study to elucidate the underlying genetic determinants in EA contributing to this variability in blood pressure (BP)...
Autores principales: | , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
John Wiley and Sons Inc.
2019
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6742943/ https://www.ncbi.nlm.nih.gov/pubmed/31033190 http://dx.doi.org/10.1111/cts.12643 |
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author | Singh, Sonal El Rouby, Nihal McDonough, Caitrin W. Gong, Yan Bailey, Kent R. Boerwinkle, Eric Chapman, Arlene B. Gums, John G. Turner, Stephen T. Cooper‐DeHoff, Rhonda M. Johnson, Julie A. |
author_facet | Singh, Sonal El Rouby, Nihal McDonough, Caitrin W. Gong, Yan Bailey, Kent R. Boerwinkle, Eric Chapman, Arlene B. Gums, John G. Turner, Stephen T. Cooper‐DeHoff, Rhonda M. Johnson, Julie A. |
author_sort | Singh, Sonal |
collection | PubMed |
description | European Americans (EA) have a better antihypertensive response to β‐blockers when compared with African Americans, albeit with some variability. We undertook a genomewide association study to elucidate the underlying genetic determinants in EA contributing to this variability in blood pressure (BP) response. A discovery genomewide association study of change in BP post–metoprolol treatment was performed in EA participants (n = 201) from the Pharmacogenomic Evaluation of Antihypertensive Responses‐2 (PEAR‐2) study and tested for replication in the atenolol‐treated EA from the PEAR study (n = 233). Rs294610 in the FGD5, which encodes for FYVE, RhoGEF and PH Domain Containing 5, (expression quantitative trait loci for FGD5 in the small intestine) was significantly associated with increased diastolic BP response to β‐blockers in the PEAR‐2 study (P = 3.41 × 10(−6), β = −2.70) and replicated (P = 0.01, β = −1.17) in the PEAR study. Post–meta‐analysis of these studies, an additional single nucleotide polymorphism rs45545233 in the SLC4A1, encoding for Solute Carrier Family 4 Member 1, (expression quantitative trait loci for dual specificity phosphatase 3 in the artery tibial) was identified that was significantly associated with a poor response to β‐blockers (P = 3.43 × 10(−6), β = 4.57) and was replicated in the atenolol add‐on cohort (P = 0.007, β = 4.97). We identified variants in FGD5 and SLC4A1, which have been previously cited as candidate genes for hypertension, to be associated with a β‐blocker BP response in EA. Further elucidation is warranted of the underlying mechanisms of these variants and genes by which they influence the BP response to β‐blockers. |
format | Online Article Text |
id | pubmed-6742943 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | John Wiley and Sons Inc. |
record_format | MEDLINE/PubMed |
spelling | pubmed-67429432019-09-14 Genomic Association Analysis Reveals Variants Associated With Blood Pressure Response to Beta‐Blockers in European Americans Singh, Sonal El Rouby, Nihal McDonough, Caitrin W. Gong, Yan Bailey, Kent R. Boerwinkle, Eric Chapman, Arlene B. Gums, John G. Turner, Stephen T. Cooper‐DeHoff, Rhonda M. Johnson, Julie A. Clin Transl Sci Research European Americans (EA) have a better antihypertensive response to β‐blockers when compared with African Americans, albeit with some variability. We undertook a genomewide association study to elucidate the underlying genetic determinants in EA contributing to this variability in blood pressure (BP) response. A discovery genomewide association study of change in BP post–metoprolol treatment was performed in EA participants (n = 201) from the Pharmacogenomic Evaluation of Antihypertensive Responses‐2 (PEAR‐2) study and tested for replication in the atenolol‐treated EA from the PEAR study (n = 233). Rs294610 in the FGD5, which encodes for FYVE, RhoGEF and PH Domain Containing 5, (expression quantitative trait loci for FGD5 in the small intestine) was significantly associated with increased diastolic BP response to β‐blockers in the PEAR‐2 study (P = 3.41 × 10(−6), β = −2.70) and replicated (P = 0.01, β = −1.17) in the PEAR study. Post–meta‐analysis of these studies, an additional single nucleotide polymorphism rs45545233 in the SLC4A1, encoding for Solute Carrier Family 4 Member 1, (expression quantitative trait loci for dual specificity phosphatase 3 in the artery tibial) was identified that was significantly associated with a poor response to β‐blockers (P = 3.43 × 10(−6), β = 4.57) and was replicated in the atenolol add‐on cohort (P = 0.007, β = 4.97). We identified variants in FGD5 and SLC4A1, which have been previously cited as candidate genes for hypertension, to be associated with a β‐blocker BP response in EA. Further elucidation is warranted of the underlying mechanisms of these variants and genes by which they influence the BP response to β‐blockers. John Wiley and Sons Inc. 2019-06-04 2019-09 /pmc/articles/PMC6742943/ /pubmed/31033190 http://dx.doi.org/10.1111/cts.12643 Text en © 2019 The Authors. Clinical and Translational Science published by Wiley Periodicals, Inc. on behalf of the American Society for Clinical Pharmacology and Therapeutics. This is an open access article under the terms of the http://creativecommons.org/licenses/by-nc/4.0/ License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes. |
spellingShingle | Research Singh, Sonal El Rouby, Nihal McDonough, Caitrin W. Gong, Yan Bailey, Kent R. Boerwinkle, Eric Chapman, Arlene B. Gums, John G. Turner, Stephen T. Cooper‐DeHoff, Rhonda M. Johnson, Julie A. Genomic Association Analysis Reveals Variants Associated With Blood Pressure Response to Beta‐Blockers in European Americans |
title | Genomic Association Analysis Reveals Variants Associated With Blood Pressure Response to Beta‐Blockers in European Americans |
title_full | Genomic Association Analysis Reveals Variants Associated With Blood Pressure Response to Beta‐Blockers in European Americans |
title_fullStr | Genomic Association Analysis Reveals Variants Associated With Blood Pressure Response to Beta‐Blockers in European Americans |
title_full_unstemmed | Genomic Association Analysis Reveals Variants Associated With Blood Pressure Response to Beta‐Blockers in European Americans |
title_short | Genomic Association Analysis Reveals Variants Associated With Blood Pressure Response to Beta‐Blockers in European Americans |
title_sort | genomic association analysis reveals variants associated with blood pressure response to beta‐blockers in european americans |
topic | Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6742943/ https://www.ncbi.nlm.nih.gov/pubmed/31033190 http://dx.doi.org/10.1111/cts.12643 |
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