FKBP5 methylation as a possible marker for cortisol state and transient cortisol exposure in healthy human subjects

Abstract

Current glucocorticoid replacement regimens, in adrenal insufficiency, fail to mimic the physiological cortisol secretion, thereby fostering serious side effects. Aim: To experimentally evaluate the impact of CpG methylation within the FKBP5 gene as a possible short- and long-term marker for cortisol exposure in humans. Materials & methods: An ACTH-stimulation test was carried out and methylation status of the FKBP5 gene in leukocytes was determined. Results: A negative correlation between basal levels of methylation and serum cortisol was observed. Individual changes in FKBP5 methylation after 24 h correlated with cortisol responses. Conclusion: Considering previous studies conducted with murine leucocytes, FKBP5 methylation may be suitable as a long-term biomarker, rather than acute glucocorticoid exposure, also in humans.

Keywords::

• ACTH stimulation test
• demethylation
• FKBP5
• glucocorticoid exposure
• hydrocortisone

Financial & competing interests disclosure

H Oster has a Lichtenberg fellowship of the Volkswagen Foundation. H Kirchner is funded by the Emmy-Noether Programm of the German Research Foundation (DFG). B Harbeck received a research grant by the University of Luebeck. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

No writing assistance was utilized in the production of this manuscript.

Additional information

Funding

H Oster has a Lichtenberg fellowship of the Volkswagen Foundation. H Kirchner is funded by the Emmy-Noether Programm of the German Research Foundation (DFG). B Harbeck received a research grant by the University of Luebeck. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed. No writing assistance was utilized in the production of this manuscript.