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Eur J Clin Invest. 2019 May 15:e13129. doi: 10.1111/eci.13129. [Epub ahead of print]

Transcriptomics in tissue glucocorticoid sensitivity.

Author information

1
Division of Endocrinology, Metabolism and Diabetes, First Department of Pediatrics, University of Athens Medical School, "Aghia Sophia" Children's Hospital, Athens, Greece.
2
Division of Endocrinology and Metabolism, Center for Clinical, Experimental Surgery & Translational Research, Biomedical Research Foundation of the Academy of Athens, Athens, Greece.
3
Institute of Molecular Biology, Genetics and Biotechnology, Biomedical Research Foundation of the Academy of Athens, Athens, Greece.

Abstract

BACKGROUND:

Synthetic glucocorticoids are widely used in the treatment of several inflammatory, autoimmune and lymphoproliferative disorders. However, considerable variation in response to therapeutic doses of glucocorticoids has been documented among individuals. The aim of our study was to identify novel glucocorticoid sensitivity-determining genes using genome-wide expression profiling in healthy subjects.

METHODS:

One hundred one healthy subjects [mean age ± standard error of the mean (SEM); 26.52 ± 0.50 years] were given 0.25 mg dexamethasone at midnight, and serum cortisol concentrations were determined at 08:00 hours the following morning. Subjects were stratified into the 10% most glucocorticoid-sensitive and 10% most glucocorticoid-resistant according to the serum cortisol concentrations. Genomic DNA, RNA and plasma samples were obtained in the 22 subjects one month later.

RESULTS:

Transcriptomic analysis showed variability between glucocorticoid-resistant and glucocorticoid-sensitive subjects. One hundred thirty-three genes were upregulated and 49 downregulated in the glucocorticoid-resistant compared to the glucocorticoid-sensitive group. Further analysis revealed differences between 3 glucocorticoid-resistant and 3 glucocorticoid-sensitive subjects. The majority of the 1058 upregulated genes and 1139 downregulated genes were found to participate in telomere maintenance, systemic lupus erythematosus and Alzheimer's disease. Interestingly, Synuclein A, a key molecule in Parkinson's disease, was upregulated in the subgroup of glucocorticoid-sensitive subjects.

CONCLUSIONS:

We have identified differences in tissue sensitivity to glucocorticoids among healthy subjects at the transcriptomic level. These differences are associated with differential expression of genes related to autoimmune and neurological disorders.

KEYWORDS:

RNA sequencing; glucocorticoid receptor; glucocorticoids; telomere length; tissue glucocorticoid sensitivity; transcriptomics

PMID:
31091335
DOI:
10.1111/eci.13129

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