Evidence map›Paper›PMID 25622599›Full record

Trial reportJournal of the American Heart Association2015

Pharmacogenomics of hypertension: a genome‐wide, placebo‐controlled cross‐over study, using four classes of antihypertensive drugs.

Timo P Hiltunen, Kati M Donner, Antti-Pekka Sarin, Janna Saarela, Samuli Ripatti, Arlene B Chapman, John G Gums, Yan Gong, Rhonda M Cooper-DeHoff, Francesca Frau and 8 more

Registry-linked trialOpen access · goldAbstract readComparative StudyRandomized Controlled Trial
In one paragraph

Trial report in Journal of the American Heart Association, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT03276598 (A Randomised Double-blind Cross-over Single-centre Study on Molecular Genetics of Drug Responsiveness in Essential Hypertension), which is not on this map. Cited by 43 papers, 4 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
43citing papers in PubMed, 4 pooled it
1.0field-weighted citation impact, top 20% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

NCT03276598 phase4completednot on this map

A Randomised Double-blind Cross-over Single-centre Study on Molecular Genetics of Drug Responsiveness in Essential Hypertension

TypeinterventionalSponsorHelsinki University Central HospitalRan1999 to 2004Enrolled233ConditionsHypertension, PharmacogeneticsArmsAmlodipine, Bisoprolol, Hydrochlorothiazide, Losartan, Placebo
3 · Its place in the literature

Who cites it

43 citing papers in PubMed, 4 syntheses or guidelines pooled it, 14 citations in OpenAlex.

  1. Pooled it
  2. Pooled it
  3. Genome-Wide Meta-Analysis of Blood Pressure Response to βJournal of the American Heart Association · 2019
    Pooled it
  4. Pooled it
  5. Trial
  6. Trial
  7. Trial
  8. Trial
  9. Influence ofAnnals of medicine · 2026
    Article
  10. Review
  11. Article
  12. Review
  13. American journal of cardiovascular disease · 2023
    Article
  14. Review
  15. Article
  16. Article
  17. Article
  18. Pharmacogenomics Informs Cardiovascular Pharmacotherapy.Methods in molecular biology (Clifton, N.J.) · 2022
    Article
  19. Article
  20. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

18 authors at 2 institutions in 1 country.

Timo P Hiltunen
Kati M Donner
Antti-Pekka Sarin
Janna Saarela
Samuli Ripatti
Arlene B Chapman
John G Gums
Yan Gong
Rhonda M Cooper-DeHoff
Francesca Frau
Valeria Glorioso
Roberta Zaninello
Erika Salvi
Nicola Glorioso
Eric Boerwinkle
Stephen T Turner
Julie A Johnson
Kimmo K Kontula
Harvard University · USUMass Memorial Medical Center · US

Funding

Mayo Clinic Center for Translational Science ActivitiesUL1TR000135 · NCATS · MAYO CLINIC ROCHESTER · PI KHOSLA, SUNDEEP · 2012 to 2015
$41.2M
Using social networks to map and evaluate team science across CTSA hubsUL1TR001427 · NCATS · UNIVERSITY OF FLORIDA · PI MITCHELL, DUANE A. · 2015 to 2024
$37.2M
Atlanta Clinical and Translational Science Institute (ACTSI) RenewalUL1TR000454 · NCATS · EMORY UNIVERSITY · PI STEPHENS, DAVID S · 2012 to 2016
$25.8M
Pharmacogenomic Evaluation of Antihypertensive ResponsesU01GM074492 · NIGMS · UNIVERSITY OF FLORIDA · PI COOPER-DEHOFF, RHONDA M, JOHNSON, JULIE A. · 2005 to 2014
$20.7M
UF Clinical and Translational Science AwardUL1TR000064 · NCATS · UNIVERSITY OF FLORIDA · PI NELSON, DAVID R · 2012 to 2014
$12.2M
Anthipertensive PharmacoGenomicsR01HL074735 · NHLBI · MAYO CLINIC ROCHESTER · PI TURNER, STEPHEN T · 2003 to 2006
$3.4M
NCATS NIH HHS UL1 TR000064NCATS NIH HHS UL1TR000064NCATS NIH HHS UL1 TR000135NCATS NIH HHS UL1 TR000454NCATS NIH HHS UL1 TR001427NHLBI NIH HHS R01 HL053335NHLBI NIH HHS R01 HL074735NIGMS NIH HHS U01 GM074492NIGMS NIH HHS U01-GM074492
6 · The paper itself

Abstract

backgroundIdentification of genetic markers of antihypertensive drug responses could assist in individualization of hypertension treatment. METHODS AND

resultsWe conducted a genome-wide association study to identify gene loci influencing the responsiveness of 228 male patients to 4 classes of antihypertensive drugs. The Genetics of Drug Responsiveness in Essential Hypertension (GENRES) study is a double-blind, placebo-controlled cross-over study where each subject received amlodipine, bisoprolol,hydrochlorothiazide, and losartan, each as a monotherapy, in a randomized order. Replication analyses were performed in 4 studies with patients of European ancestry (PEAR Study, N=386; GERA I and II Studies, N=196 and N=198; SOPHIA Study, N=372). We identified 3 single-nucleotide polymorphisms within the ACY3 gene that showed associations with bisoprolol response reaching genome-wide significance (P<5x10(-8))however, this could not be replicated in the PEAR Study using atenolol. In addition, 39 single-nucleotide polymorphisms showed P values of 10(-5) to 10(-7). The 20 top-associated single-nucleotide polymorphisms were different for each antihypertensive drug. None of these top single-nucleotide polymorphisms co-localized with the panel of >40 genes identified in genome-wide association studies of hypertension. Replication analyses of GENRES results provided suggestive evidence for a missense variant (rs3814995) in the NPHS1 (nephrin) gene influencing losartan response, and for 2 variants influencing hydrochlorothiazide response, located within or close to the ALDH1A3 (rs3825926) and CLIC5 (rs321329) genes.

conclusionsThese data provide some evidence for a link between biology of the glomerular protein nephrin and antihypertensive action of angiotensin receptor antagonists and encourage additional studies on aldehyde dehydrogenase–mediated reactions in antihypertensive drug action.

Indexed as

AdultAldehyde OxidoreductasesAmlodipineAntihypertensive AgentsBenzimidazolesBiphenyl CompoundsBisoprololBlood Pressure Monitoring, AmbulatoryChloride ChannelsCross-Over StudiesDose-Response Relationship, DrugDouble-Blind MethodDrug Administration ScheduleEssential HypertensionFinlandGenome-Wide Association Studyaldehyde dehydrogenase (NAD(P)+)Aldehyde OxidoreductasesAmlodipineAntihypertensive AgentsBenzimidazolesBiphenyl CompoundsBisoprololcandesartanChloride ChannelsCLIC5 protein, humanHydrochlorothiazideLosartanMembrane ProteinsMicrofilament ProteinsnephrinTetrazoles

Identifiers

PMID25622599
PMCPMC4330076
OpenAlexW2125700511

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC
Read underepoch 390

Registered trials

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.