z-logo
open-access-imgOpen Access
Genomic Association Analysis Reveals Variants Associated With Blood Pressure Response to Beta‐Blockers in European Americans
Author(s) -
Singh Sonal,
El Rouby Nihal,
McDonough Caitrin W.,
Gong Yan,
Bailey Kent R.,
Boerwinkle Eric,
Chapman Arlene B.,
Gums John G.,
Turner Stephen T.,
CooperDeHoff Rhonda M.,
Johnson Julie A.
Publication year - 2019
Publication title -
clinical and translational science
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.303
H-Index - 44
eISSN - 1752-8062
pISSN - 1752-8054
DOI - 10.1111/cts.12643
Subject(s) - beta (programming language) , medicine , blood pressure , genetics , biology , bioinformatics , computer science , programming language
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 FGD 5 , which encodes for FYVE, RhoGEF and PH Domain Containing 5, ( expression quantitative trait loci for FGD 5 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 SLC 4A1 , 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 FGD 5 and SLC 4A1 , 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.

The content you want is available to Zendy users.

Already have an account? Click here to sign in.
Having issues? You can contact us here