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

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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
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Description
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. (2020-10-21)
Subject Medicine, Health and Life Sciences
Keyword Addison's disease, Biomarkers, Glucocorticoid, Adrenal insufficiency, Gene expression
Related Publication 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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Published Dec 8, 2020
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MD5: 84642f7fc4bb6f4117f82ab3bda602f9
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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Published Dec 8, 2020
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MD5: cdbbbb237e3b141576d2de3d159ffdb4
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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Published Dec 8, 2020
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MD5: 12bc45c88cd56a985841573e46021ead
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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