Replication data for: Potential Transcriptional Biomarkers to Guide Glucocorticoid Replacement in Autoimmune Addison’s Disease (doi:10.18710/Q3FZAN)

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Replication data for: Potential Transcriptional Biomarkers to Guide Glucocorticoid Replacement in Autoimmune Addison’s Disease

doi:10.18710/Q3FZAN

DataverseNO

2020-12-08

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Sævik, Åse Bjorvatn, 2020, "Replication data for: Potential Transcriptional Biomarkers to Guide Glucocorticoid Replacement in Autoimmune Addison’s Disease", https://doi.org/10.18710/Q3FZAN, DataverseNO, V1

Replication data for: Potential Transcriptional Biomarkers to Guide Glucocorticoid Replacement in Autoimmune Addison’s Disease

doi:10.18710/Q3FZAN

Sævik, Åse Bjorvatn (University of Bergen)

Wollf, Anette

Dolan, David

Øksnes, Marianne

Løvås, Kristian

University of Bergen

Applied Biosystems 1700 Expression Array system

270068

288022

DataverseNO

University of Bergen

Sævik, Åse Bjorvatn

Sævik, Åse Bjorvatn

2020-10-21

https://doi.org/10.18710/Q3FZAN

Medicine, Health and Life Sciences, Addison's disease, Biomarkers, Glucocorticoid, Adrenal insufficiency, Gene expression

Background: No 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. Objective: To explore changes in gene expression following different GC replacement doses as a means of identifying candidate transcriptional biomarkers to guide GC replacement in AAD. Methods: Step 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 three of the most highly upregulated genes, we performed real-time PCR (rt-PCR) to compare gene expression levels before and two, four, and six 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. Results: Step 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 ADARB1, ARIDB5, and POU2F1 decreased in normal versus very low morning cortisol. Normal serum cortisol levels positively correlated with DSIPI, DDIT4, and FKBP5 expression. Conclusions: We 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.

2007-2014

Norway

Blood samples: RNA expression microarray

Gene names

Submitted manuscript (December 2020) to The Journal of the Endocrine Society (JES) # js.2020-00396: "Potential Transcriptional Biomarkers to Guide Glucocorticoid Replacement in Autoimmune Addisonæs Disease”)

Submitted manuscript (December 2020) to The Journal of the Endocrine Society (JES) # js.2020-00396: "Potential Transcriptional Biomarkers to Guide Glucocorticoid Replacement in Autoimmune Addisonæs Disease”)

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0_ReadMe.txt

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ReadMe file with description of the content of .txt-files "Transcriptional_Biomarkers_Addison_Step1" and "Transcriptional_Biomarkers_Addison_Step2"

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Transcriptional_Biomarkers_Addison_Step1.txt

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Step 1: The 150 most up-regulated genes in leukocytes in the global transcriptional analysis in blood using RNA expression microarray

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Transcriptional_Biomarkers_Addison_Step2.txt

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Step 2: List of the 93 included genes for comparison of expression levels in normal compared to very low cortisol levels.

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