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

Ana Caroline C. Sá, Amy Webb, Yan Gong, Caitrin W. McDonough, Mohamed H. Shahin, Somnath Datta, Taimour Y. Langaee, Stephen T Turner, Amber L. Beitelshees, Arlene B. Chapman, Eric Boerwinkle, John G. Gums, Steven E. Scherer, Rhonda M. Cooper-Dehoff, Wolfgang Sadee, Julie A. Johnson

Research output: Contribution to journalArticle

2 Citations (Scopus)

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.

Original languageEnglish (US)
Article number55
JournalBMC Medical Genomics
Volume11
Issue number1
DOIs
StatePublished - Jun 20 2018

Fingerprint

Sodium Chloride Symporter Inhibitors
Pharmacogenetics
Antihypertensive Agents
Blood Pressure
Hydrochlorothiazide
Genes
Chlorthalidone
Hypertension
RNA Sequence Analysis
Chromosomes, Human, Pair 12
Meta-Analysis
Cohort Studies

Keywords

  • eQTL
  • Hypertension
  • Personalized medicine
  • Pharmacogenomics
  • RNA-Seq
  • Thiazide diuretics

ASJC Scopus subject areas

  • Genetics
  • Genetics(clinical)

Cite this

Sá, A. C. C., Webb, A., Gong, Y., McDonough, C. W., Shahin, M. H., Datta, S., ... Johnson, J. A. (2018). Blood pressure signature genes and blood pressure response to thiazide diuretics: Results from the PEAR and PEAR-2 studies. BMC Medical Genomics, 11(1), [55]. https://doi.org/10.1186/s12920-018-0370-x

Blood pressure signature genes and blood pressure response to thiazide diuretics : Results from the PEAR and PEAR-2 studies. / Sá, Ana Caroline C.; Webb, Amy; Gong, Yan; McDonough, Caitrin W.; Shahin, Mohamed H.; Datta, Somnath; Langaee, Taimour Y.; Turner, Stephen T; Beitelshees, Amber L.; Chapman, Arlene B.; Boerwinkle, Eric; Gums, John G.; Scherer, Steven E.; Cooper-Dehoff, Rhonda M.; Sadee, Wolfgang; Johnson, Julie A.

In: BMC Medical Genomics, Vol. 11, No. 1, 55, 20.06.2018.

Research output: Contribution to journalArticle

Sá, ACC, Webb, A, Gong, Y, McDonough, CW, Shahin, MH, Datta, S, Langaee, TY, Turner, ST, Beitelshees, AL, Chapman, AB, Boerwinkle, E, Gums, JG, Scherer, SE, Cooper-Dehoff, RM, Sadee, W & Johnson, JA 2018, 'Blood pressure signature genes and blood pressure response to thiazide diuretics: Results from the PEAR and PEAR-2 studies', BMC Medical Genomics, vol. 11, no. 1, 55. https://doi.org/10.1186/s12920-018-0370-x
Sá, Ana Caroline C. ; Webb, Amy ; Gong, Yan ; McDonough, Caitrin W. ; Shahin, Mohamed H. ; Datta, Somnath ; Langaee, Taimour Y. ; Turner, Stephen T ; Beitelshees, Amber L. ; Chapman, Arlene B. ; Boerwinkle, Eric ; Gums, John G. ; Scherer, Steven E. ; Cooper-Dehoff, Rhonda M. ; Sadee, Wolfgang ; Johnson, Julie A. / Blood pressure signature genes and blood pressure response to thiazide diuretics : Results from the PEAR and PEAR-2 studies. In: BMC Medical Genomics. 2018 ; Vol. 11, No. 1.
@article{33296e783e15471caf2f742a011e94c7,
title = "Blood pressure signature genes and blood pressure response to thiazide diuretics: Results from the PEAR and PEAR-2 studies",
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.",
keywords = "eQTL, Hypertension, Personalized medicine, Pharmacogenomics, RNA-Seq, Thiazide diuretics",
author = "S{\'a}, {Ana Caroline C.} and Amy Webb and Yan Gong and McDonough, {Caitrin W.} and Shahin, {Mohamed H.} 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.}",
year = "2018",
month = "6",
day = "20",
doi = "10.1186/s12920-018-0370-x",
language = "English (US)",
volume = "11",
journal = "BMC Medical Genomics",
issn = "1755-8794",
publisher = "BioMed Central",
number = "1",

}

TY - JOUR

T1 - Blood pressure signature genes and blood pressure response to thiazide diuretics

T2 - Results from the PEAR and PEAR-2 studies

AU - Sá, Ana Caroline C.

AU - Webb, Amy

AU - Gong, Yan

AU - McDonough, Caitrin W.

AU - Shahin, Mohamed H.

AU - Datta, Somnath

AU - Langaee, Taimour Y.

AU - Turner, Stephen T

AU - Beitelshees, Amber L.

AU - Chapman, Arlene B.

AU - Boerwinkle, Eric

AU - Gums, John G.

AU - Scherer, Steven E.

AU - Cooper-Dehoff, Rhonda M.

AU - Sadee, Wolfgang

AU - Johnson, Julie A.

PY - 2018/6/20

Y1 - 2018/6/20

N2 - 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.

AB - 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.

KW - eQTL

KW - Hypertension

KW - Personalized medicine

KW - Pharmacogenomics

KW - RNA-Seq

KW - Thiazide diuretics

UR - http://www.scopus.com/inward/record.url?scp=85048751043&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85048751043&partnerID=8YFLogxK

U2 - 10.1186/s12920-018-0370-x

DO - 10.1186/s12920-018-0370-x

M3 - Article

C2 - 29925376

AN - SCOPUS:85048751043

VL - 11

JO - BMC Medical Genomics

JF - BMC Medical Genomics

SN - 1755-8794

IS - 1

M1 - 55

ER -