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Potential Transcrip...
Potential Transcriptional Biomarkers to Guide Glucocorticoid Replacement in Autoimmune Addison's Disease
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- Bjorvatn Saevik, Åse (författare)
- Univ Bergen, Dept Clin Sci, Lab Bldg, 8th Floor, Jonas Lies Vei 91B, N-5021 Bergen, Norway; Univ Bergen, KG Jebsen Ctr Autoimmune Disorders, NO-5021 Bergen, Norway
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- Wolff, Anette B. (författare)
- Univ Bergen, Dept Clin Sci, Lab Bldg, 8th Floor, Jonas Lies Vei 91B, N-5021 Bergen, Norway; Univ Bergen, KG Jebsen Ctr Autoimmune Disorders, NO-5021 Bergen, Norway
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- Björnsdottir, Sigridur (författare)
- Karolinska Inst, Dept Mol Med & Surg, S-17177 Stockholm, Sweden; Karolinska Univ Hosp, Dept Endocrinol, S-17177 Stockholm, Sweden
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- Simunkova, Katerina (författare)
- Univ Bergen, Dept Clin Sci, Lab Bldg, 8th Floor, Jonas Lies Vei 91B, N-5021 Bergen, Norway
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- Schei Hynne, Martha (författare)
- Univ Bergen, Dept Clin Sci, Lab Bldg, 8th Floor, Jonas Lies Vei 91B, N-5021 Bergen, Norway
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- Dolan, David William Peter (författare)
- Univ Bergen, Dept Informat, N-5020 Bergen, Norway
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- Bratland, Eirik (författare)
- Univ Bergen, Dept Clin Sci, Lab Bldg, 8th Floor, Jonas Lies Vei 91B, N-5021 Bergen, Norway; Univ Bergen, KG Jebsen Ctr Autoimmune Disorders, NO-5021 Bergen, Norway; Haukeland Hosp, Dept Med Genet, NO-5021 Bergen, Norway
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- Knappskog, Per M. (författare)
- Univ Bergen, KG Jebsen Ctr Autoimmune Disorders, NO-5021 Bergen, Norway; Haukeland Hosp, Dept Med Genet, NO-5021 Bergen, Norway
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- Methlie, Paal (författare)
- Univ Bergen, Dept Clin Sci, Lab Bldg, 8th Floor, Jonas Lies Vei 91B, N-5021 Bergen, Norway; Univ Bergen, KG Jebsen Ctr Autoimmune Disorders, NO-5021 Bergen, Norway; Haukeland Hosp, Dept Med, NO-5021 Bergen, Norway
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- Carlsen, Siri (författare)
- Stavanger Univ Hosp, Dept Endocrinol, N-4068 Stavanger, Norway
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- Isaksson, Magnus (författare)
- Uppsala universitet,Endokrinologi och mineralmetabolism
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- Bensing, Sophie (författare)
- Karolinska Institutet
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- Kämpe, Olle (författare)
- Karolinska Institutet
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- Husebye, Eystein S. (författare)
- Univ Bergen, Dept Clin Sci, Lab Bldg, 8th Floor, Jonas Lies Vei 91B, N-5021 Bergen, Norway; Univ Bergen, KG Jebsen Ctr Autoimmune Disorders, NO-5021 Bergen, Norway; Haukeland Hosp, Dept Med, NO-5021 Bergen, Norway; Karolinska Univ Hosp, Karolinska Inst, Dept Med Solna, S-17177 Stockholm, Sweden
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- Løvås, Kristian (författare)
- Univ Bergen, Dept Clin Sci, Lab Bldg, 8th Floor, Jonas Lies Vei 91B, N-5021 Bergen, Norway; Univ Bergen, KG Jebsen Ctr Autoimmune Disorders, NO-5021 Bergen, Norway; Haukeland Hosp, Dept Med, NO-5021 Bergen, Norway
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- Øksnes, Marianne (författare)
- Univ Bergen, Dept Clin Sci, Lab Bldg, 8th Floor, Jonas Lies Vei 91B, N-5021 Bergen, Norway; Univ Bergen, KG Jebsen Ctr Autoimmune Disorders, NO-5021 Bergen, Norway; Karolinska Univ Hosp, Dept Endocrinol, S-17177 Stockholm, Sweden; Haukeland Hosp, Dept Med, NO-5021 Bergen, Norway
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(creator_code:org_t)
- 2021-01-04
- 2021
- Engelska.
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Ingår i: Journal of the Endocrine Society. - : Endocrine Society. - 2472-1972. ; 5:3
- Relaterad länk:
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https://doi.org/10.1...
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Abstract
Ämnesord
Stäng
- BackgroundNo reliable biomarkers exist to guide glucocorticoid (GC) replacement treatment in autoimmune Addison’s disease (AAD), leading to overtreatment with alarming and persistent side effects or undertreatment, which could be fatal.ObjectiveTo explore changes in gene expression following different GC replacement doses as a means of identifying candidate transcriptional biomarkers to guide GC replacement in AAD.MethodsStep 1: Global microarray expression analysis on RNA from whole blood before and after intravenous infusion of 100 mg hydrocortisone (HC) in 10 patients with AAD. In 3 of the most highly upregulated genes, we performed real-time PCR (rt-PCR) to compare gene expression levels before and 3, 4, and 6 hours after the HC infusion. Step 2: Rt-PCR to compare expression levels of 93 GC-regulated genes in normal versus very low morning cortisol levels in 27 patients with AAD.ResultsStep 1: Two hours after infusion of 100 mg HC, there was a marked increase in FKBP5, MMP9, and DSIPI expression levels. MMP9 and DSIPI expression levels correlated with serum cortisol. Step 2: Expression levels of CEBPB, DDIT4, FKBP5, DSIPI, and VDR were increased and levels of ADARB1, ARIDB5, and POU2F1 decreased in normal versus very low morning cortisol. Normal serum cortisol levels positively correlated with DSIPI, DDIT4, and FKBP5 expression.ConclusionsWe introduce gene expression as a novel approach to guide GC replacement in AAD. We suggest that gene expression of DSIPI, DDIT4, and FKBP5 are particularly promising candidate biomarkers of GC replacement, followed by MMP9, CEBPB, VDR, ADARB1, ARID5B, and POU2F1.
Ämnesord
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Endokrinologi och diabetes (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Endocrinology and Diabetes (hsv//eng)
Nyckelord
- Addison's disease
- primary adrenal insufficiency
- biomarkers
- gene expression
- glucocorticoid
Publikations- och innehållstyp
- ref (ämneskategori)
- art (ämneskategori)
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- Av författaren/redakt...
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Bjorvatn Saevik, ...
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Wolff, Anette B.
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Björnsdottir, Si ...
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Simunkova, Kater ...
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Schei Hynne, Mar ...
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Dolan, David Wil ...
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visa fler...
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Bratland, Eirik
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Knappskog, Per M ...
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Methlie, Paal
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Carlsen, Siri
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Isaksson, Magnus
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Bensing, Sophie
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Kämpe, Olle
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Husebye, Eystein ...
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Løvås, Kristian
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Øksnes, Marianne
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- Om ämnet
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- MEDICIN OCH HÄLSOVETENSKAP
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MEDICIN OCH HÄLS ...
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och Klinisk medicin
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och Endokrinologi oc ...
- Artiklar i publikationen
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Journal of the E ...
- Av lärosätet
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Uppsala universitet
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Karolinska Institutet