@article{5df5618b333f4cdaa84e74f58a10266b,
title = "Whole Transcriptome Sequencing Analyses Reveal Molecular Markers of Blood Pressure Response to Thiazide Diuretics",
abstract = "Thiazide diuretics (TD) are commonly prescribed anti-hypertensives worldwide. However, <40% of patients treated with thiazide monotherapy achieve BP control. This study uses whole transcriptome sequencing to identify novel molecular markers associated with BP response to TD. We assessed global RNA expression levels in whole blood samples from 150 participants, representing patients in the upper and lower quartile of BP response to TD from the Pharmacogenomic Evaluation of Antihypertensive Responses (PEAR) (50 whites) and from PEAR-2 (50 whites and 50 blacks). In each study cohort, we performed poly-A RNA-sequencing in baseline samples from 25 responders and 25 non-responders to hydrochlorothiazide (HCTZ) or chlorthalidone. At FDR adjusted p-value < 0.05, 29 genes were differentially expressed in relation to HCTZ or chlorthalidone BP response in whites. For each differentially expressed gene, replication was attempted in the alternate white group and PEAR-2 blacks. CEBPD (meta-analysis p = 1.8 × 10-11) and TSC22D3 (p = 1.9 × 10-9) were differentially expressed in all 3 cohorts, and explain, in aggregate, 21.9% of response variability to TD. This is the first report of the use of transcriptome-wide sequencing data to identify molecular markers of antihypertensive drug response. These findings support CEBPD and TSC22D3 as potential biomarkers of BP response to TD.",
author = "S{\'a}, {Ana Caroline C.} and Amy Webb and Yan Gong and McDonough, {Caitrin W.} and Somnath Datta and Langaee, {Taimour Y.} and Turner, {Stephen T.} and Beitelshees, {Amber L.} and Chapman, {Arlene B.} and Eric Boerwinkle and Gums, {John G.} and Scherer, {Steven E.} and Cooper-Dehoff, {Rhonda M.} and Wolfgang Sadee and Johnson, {Julie A.}",
note = "Funding Information: We thank the valuable contributions of the Pharmacogenomics Evaluation of Antihypertensive Responses (PEAR) study participants, support staff, and study physicians. We also thank University of Florida Research Computing (http://researchcomputing.ufl.edu) for providing computational resources and support as well as BCM-HGSC personnel including Viktoriya Korchina, HarshaVardhan Doddapaneni, Donna Muzny and Richard Gibbs that have contributed to the research results reported in this publication. 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. Publisher Copyright: {\textcopyright} 2017 The Author(s).",
year = "2017",
month = dec,
day = "1",
doi = "10.1038/s41598-017-16343-z",
language = "English (US)",
volume = "7",
journal = "Scientific Reports",
issn = "2045-2322",
publisher = "Nature Publishing Group",
number = "1",
}