Research
Print page Print page
Switch language
The Capital Region of Denmark - a part of Copenhagen University Hospital
Published

Identification of human glucocorticoid response markers using integrated multi-omic analysis from a randomized crossover trial

Research output: Contribution to journalJournal articleResearchpeer-review

DOI

  1. Cortical signatures of precision grip force control in children, adolescents, and adults

    Research output: Contribution to journalJournal articleResearchpeer-review

  2. Heterogeneous contributions of change in population distribution of body mass index to change in obesity and underweight

    Research output: Contribution to journalJournal articleResearchpeer-review

  3. An open label trial of anakinra to prevent respiratory failure in COVID-19

    Research output: Contribution to journalJournal articleResearchpeer-review

  4. Modeling transfer of vaginal microbiota from mother to infant in early life

    Research output: Contribution to journalJournal articleResearchpeer-review

  5. Host-induced spermidine production in motile Pseudomonas aeruginosa triggers phagocytic uptake

    Research output: Contribution to journalJournal articleResearchpeer-review

  1. Acute and persistent symptoms in non-hospitalized PCR-confirmed COVID-19 patients

    Research output: Contribution to journalJournal articleResearchpeer-review

  2. Alexithymia, Emotional Distress, and Perceived Quality of Life in Patients With Hashimoto's Thyroiditis

    Research output: Contribution to journalJournal articleResearchpeer-review

  3. Incidence and Clinical Presentation of Pheochromocytoma and Sympathetic Paraganglioma: A Population-based Study

    Research output: Contribution to journalJournal articleResearchpeer-review

  • Dimitrios Chantzichristos
  • Per-Arne Svensson
  • Terence Garner
  • Camilla Am Glad
  • Brian R Walker
  • Ragnhildur Bergthorsdottir
  • Oskar Ragnarsson
  • Penelope Trimpou
  • Roland H Stimson
  • Stina W Borresen
  • Ulla Feldt-Rasmussen
  • Per-Anders Jansson
  • Stanko Skrtic
  • Adam Stevens
  • Gudmundur Johannsson
View graph of relations

Background: Glucocorticoids are among the most commonly prescribed drugs, but there is no biomarker that can quantify their action. The aim of the study was to identify and validate circulating biomarkers of glucocorticoid action.

Methods: In a randomized, crossover, single-blind, discovery study, 10 subjects with primary adrenal insufficiency (and no other endocrinopathies) were admitted at the in-patient clinic and studied during physiological glucocorticoid exposure and withdrawal. A randomization plan before the first intervention was used. Besides mild physical and/or mental fatigue and salt craving, no serious adverse events were observed. The transcriptome in peripheral blood mononuclear cells and adipose tissue, plasma miRNAomic, and serum metabolomics were compared between the interventions using integrated multi-omic analysis.

Results: We identified a transcriptomic profile derived from two tissues and a multi-omic cluster, both predictive of glucocorticoid exposure. A microRNA (miR-122-5p) that was correlated with genes and metabolites regulated by glucocorticoid exposure was identified (p=0.009) and replicated in independent studies with varying glucocorticoid exposure (0.01 ≤ p≤0.05).

Conclusions: We have generated results that construct the basis for successful discovery of biomarker(s) to measure effects of glucocorticoids, allowing strategies to individualize and optimize glucocorticoid therapy, and shedding light on disease etiology related to unphysiological glucocorticoid exposure, such as in cardiovascular disease and obesity.

Funding: The Swedish Research Council (Grant 2015-02561 and 2019-01112); The Swedish federal government under the LUA/ALF agreement (Grant ALFGBG-719531); The Swedish Endocrinology Association; The Gothenburg Medical Society; Wellcome Trust; The Medical Research Council, UK; The Chief Scientist Office, UK; The Eva Madura's Foundation; The Research Foundation of Copenhagen University Hospital; and The Danish Rheumatism Association.

Clinical trial number: NCT02152553.

Original languageEnglish
Article numbere62236
JournaleLife
Volume10
ISSN2050-084X
DOIs
Publication statusPublished - 6 Apr 2021

ID: 66209853