Evidence map›Paper›PMID 35446883›Full record

Observational studyPloS one2022

Impact of medication on blood transcriptome reveals off-target regulations of beta-blockers.

Michael Rode, Kolja Nenoff, Kerstin Wirkner, Katrin Horn, Andrej Teren, Ralf Regenthal, Markus Loeffler, Joachim Thiery, Achim Aigner, Janne Pott and 2 more

Open access · goldAbstract readObservational Study
In one paragraph

Observational study in PloS one, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.

0numbers the graph read from it
0cells of the map it votes in
3citing papers in PubMed
0.6field-weighted citation impact, top 31% 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.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

3 citing papers in PubMed, 4 citations in OpenAlex.

  1. Article
  2. Review
  3. Genomes in clinical care.NPJ genomic medicine · 2024
    Review
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

12 authors at 3 institutions in 1 country.

Michael RodeInstitute for Medical Informatics, Statistics and Epidemiology, University of Leipzig, Leipzig, Germany.ORCID 0000-0003-4880-3294
Kolja NenoffInstitute for Medical Informatics, Statistics and Epidemiology, University of Leipzig, Leipzig, Germany.
Kerstin WirknerLIFE Research Center for Civilization Diseases, University of Leipzig, Leipzig, Germany.
Katrin HornInstitute for Medical Informatics, Statistics and Epidemiology, University of Leipzig, Leipzig, Germany.
Andrej TerenLIFE Research Center for Civilization Diseases, University of Leipzig, Leipzig, Germany.
Ralf RegenthalRudolf-Boehm-Institute for Pharmacology and Toxicology, Clinical Pharmacology, University of Leipzig, Leipzig, Germany.ORCID 0000-0002-7292-1859
Markus LoefflerInstitute for Medical Informatics, Statistics and Epidemiology, University of Leipzig, Leipzig, Germany.
Joachim ThieryLIFE Research Center for Civilization Diseases, University of Leipzig, Leipzig, Germany.
Achim AignerRudolf-Boehm-Institute for Pharmacology and Toxicology, Clinical Pharmacology, University of Leipzig, Leipzig, Germany.
Janne PottInstitute for Medical Informatics, Statistics and Epidemiology, University of Leipzig, Leipzig, Germany.ORCID 0000-0002-5983-5331
Holger KirstenInstitute for Medical Informatics, Statistics and Epidemiology, University of Leipzig, Leipzig, Germany.ORCID 0000-0002-3126-7950
Markus ScholzInstitute for Medical Informatics, Statistics and Epidemiology, University of Leipzig, Leipzig, Germany.
Leipzig University · DEChristian-Albrechts-Universität zu Kiel · DEKlinikum Lippe · DE

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundFor many drugs, mechanisms of action with regard to desired effects and/or unwanted side effects are only incompletely understood. To investigate possible pleiotropic effects and respective molecular mechanisms, we describe here a catalogue of commonly used drugs and their impact on the blood transcriptome. METHODS AND

resultsFrom a population-based cohort in Germany (LIFE-Adult), we collected genome-wide gene-expression data in whole blood using in Illumina HT12v4 micro-arrays (n = 3,378; 19,974 gene expression probes per individual). Expression profiles were correlated with the intake of active substances as assessed by participants' medication. This resulted in a catalogue of fourteen substances that were identified as associated with differential gene expression for a total of 534 genes. As an independent replication cohort, an observational study of patients with suspected or confirmed stable coronary artery disease (CAD) or myocardial infarction (LIFE-Heart, n = 3,008, 19,966 gene expression probes per individual) was employed. Notably, we were able to replicate differential gene expression for three active substances affecting 80 genes in peripheral blood mononuclear cells (carvedilol: 25; prednisolone: 17; timolol: 38). Additionally, using gene ontology enrichment analysis, we demonstrated for timolol a significant enrichment in 23 pathways, 19 of them including either GPER1 or PDE4B. In the case of carvedilol, we showed that, beside genes with well-established association with hypertension (GPER1, PDE4B and TNFAIP3), the drug also affects genes that are only indirectly linked to hypertension due to their effects on artery walls or their role in lipid biosynthesis.

conclusionsOur developed catalogue of blood gene expressions profiles affected by medication can be used to support both, drug repurposing and the identification of possible off-target effects.

Indexed as

HypertensionTranscriptomeAdrenergic beta-AntagonistsAdultCarvedilolHumansLeukocytes, MononuclearTimololAdrenergic beta-AntagonistsCarvedilolTimolol

Identifiers

PMID35446883
PMCPMC9022833
OpenAlexW4224257546

What OpenQuestion holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

None linked

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.