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Sci Rep. 2017 Nov 22;7(1):16068. doi: 10.1038/s41598-017-16343-z.

Whole Transcriptome Sequencing Analyses Reveal Molecular Markers of Blood Pressure Response to Thiazide Diuretics.

Author information

1
Center for Pharmacogenomics and Department of Pharmacotherapy and Translational Research, University of Florida, Gainesville, FL, USA.
2
Graduate Program in Genetics and Genomics, University of Florida, Gainesville, FL, USA.
3
Department of Biomedical Informatics, College of Medicine, The Ohio State University, Columbus, OH, USA.
4
Department of Biostatistics, University of Florida, Gainesville, FL, USA.
5
Division of Nephrology and Hypertension, Mayo Clinic, Rochester, MN, USA.
6
Division of Endocrinology, Diabetes and Nutrition, University of Maryland, Baltimore, MD, USA.
7
Department of Medicine, University of Chicago, Chicago, IL, USA.
8
Division of Epidemiology, University of Texas at Houston, Houston, TX, USA.
9
Department of Community Health and Family Medicine, University of Florida College of Medicine, Gainesville, FL, USA.
10
Human Genome Sequencing Center, Baylor College of Medicine, Houston, TX, USA.
11
Division of Cardiovascular Medicine, Department of Medicine, University of Florida College of Medicine, Gainesville, FL, USA.
12
Center for Pharmacogenomics, Department of Cancer Biology and Genetic, College of Medicine, Ohio State University, Columbus, OH, USA.
13
Center for Pharmacogenomics and Department of Pharmacotherapy and Translational Research, University of Florida, Gainesville, FL, USA. johnson@cop.ufl.edu.
14
Graduate Program in Genetics and Genomics, University of Florida, Gainesville, FL, USA. johnson@cop.ufl.edu.
15
Division of Cardiovascular Medicine, Department of Medicine, University of Florida College of Medicine, Gainesville, FL, USA. johnson@cop.ufl.edu.

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.

PMID:
29167564
PMCID:
PMC5700078
DOI:
10.1038/s41598-017-16343-z
[Indexed for MEDLINE]
Free PMC Article

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