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    Blood pressure signature genes and blood pressure response to thiazide diuretics: Results from the PEAR and PEAR-2 studies

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    Author
    Sá, A.C.C.
    Web, A.
    Gong, Y.
    Date
    2018
    Journal
    BMC Medical Genomics
    Publisher
    BioMed Central Ltd.
    Type
    Article
    
    Metadata
    Show full item record
    See at
    https://dx.doi.org/10.1186/s12920-018-0370-x
    Abstract
    Background: Recently, 34 genes had been associated with differential expression relative to blood pressure (BP)/ hypertension (HTN). We hypothesize that some of the genes associated with BP/HTN are also associated with BP response to antihypertensive treatment with thiazide diuretics. Methods: We assessed these 34 genes for association with differential expression to BP response to thiazide diuretics with RNA sequencing in whole blood samples from 150 hypertensive participants from the Pharmacogenomic Evaluation of Antihypertensive Responses (PEAR) and PEAR-2 studies. PEAR white and PEAR-2 white and black participants (n = 50 for each group) were selected based on the upper and lower quartile of BP response to hydrochlorothiazide (HCTZ) and to chlorthalidone. Results: FOS, DUSP1 and PPP1R15A were differentially expressed across all cohorts (meta-analysis p-value < 2.0 × 10− 6), and responders to HCTZ or chlorthalidone presented up-regulated transcripts. Rs11065987 in chromosome 12, a trans-eQTL for expression of FOS, PPP1R15A and other genes, is also associated with BP response to HCTZ in PEAR whites (SBP: β = − 2.1; p = 1.7 × 10− 3; DBP: β = − 1.4; p = 2.9 × 10− 3). Conclusions: These findings suggest FOS, DUSP1 and PPP1R15A as potential molecular determinants of antihypertensive response to thiazide diuretics. Trial registration: NCT00246519, NCT01203852 www.clinicaltrials.gov. Copyright 2018 The Author(s).
    Sponsors
    The Pharmacogenomics Evaluation of Antihypertensive Responses (PEAR) study was supported by the National Institute of Health Pharmacogenetics Research Network grant U01-GM074492 and the National Center for Advancing Translational Sciences under the award number UL1 TR000064 (University of Florida), UL1 TR000454 (Emory University), and UL1 TR000135 (Mayo Clinic). The PEAR study was also supported by funds from the Mayo Foundation. RNA-Seq data production was supported by the National Institutes of Health Pharmacogenetics Research Network grants U19-GM061388 and U19-GM061390.
    Keyword
    eQTL
    Hypertension
    Personalized medicine
    Pharmacogenomics
    RNA-Seq
    Thiazide diuretics
    Identifier to cite or link to this item
    https://www.scopus.com/inward/record.uri?eid=2-s2.0-85048751043&doi=10.1186%2fs12920-018-0370-x&partnerID=40&md5=f478e52ab79399a8ccc6e88ca45328cb; http://hdl.handle.net/10713/9687
    ae974a485f413a2113503eed53cd6c53
    10.1186/s12920-018-0370-x
    Scopus Count
    Collections
    UMB Open Access Articles 2018

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