Abstract
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Eur J Clin Invest. 2019 Aug;49(8):e13129. doi: 10.1111/eci.13129. Epub 2019 May 30.
Transcriptomics in tissue glucocorticoid sensitivity.
Nicolaides NC(1)(2), Polyzos A(3), Koniari E(1), Lamprokostopoulou A(2), Papageorgiou I(1), Golfinopoulou E(1), Papathanasiou C(1), Sertedaki A(1), Thanos D(3), Chrousos GP(1)(2), Charmandari E(1)(2).
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.
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-resi