Genome-wide DNA methylation investigation of glucocorticoid exposure within buccal samples.

Autor: Braun PR; Department of Psychiatry, Carver College of Medicine, University of Iowa, Iowa City, USA.; Department of Psychiatry and Behavioral Science, School of Medicine, Johns Hopkins University, Baltimore, USA., Tanaka-Sahker M; Department of Psychiatry, Carver College of Medicine, University of Iowa, Iowa City, USA., Chan AC; Department of Psychiatry, Carver College of Medicine, University of Iowa, Iowa City, USA., Jellison SS; Department of Psychiatry, Carver College of Medicine, University of Iowa, Iowa City, USA., Klisares MJ; Department of Psychiatry, Carver College of Medicine, University of Iowa, Iowa City, USA., Hing BW; Department of Psychiatry, Carver College of Medicine, University of Iowa, Iowa City, USA., Shabbir Y; Department of Psychiatry, Carver College of Medicine, University of Iowa, Iowa City, USA., Gaul LN; Department of Psychiatry, Carver College of Medicine, University of Iowa, Iowa City, USA., Nagahama Y; Department of Neurosurgery, Carver College of Medicine, University of Iowa, Iowa City, USA., Robles J; Department of Psychiatry, Carver College of Medicine, University of Iowa, Iowa City, USA., Heinzman JT; Department of Psychiatry, Carver College of Medicine, University of Iowa, Iowa City, USA., Sabbagh S; Department of Psychiatry, Carver College of Medicine, University of Iowa, Iowa City, USA., Cramer EM; Department of Psychiatry, Carver College of Medicine, University of Iowa, Iowa City, USA., Duncan GN; Department of Psychiatry, Carver College of Medicine, University of Iowa, Iowa City, USA., Yuki K; Department of Psychiatry, Carver College of Medicine, University of Iowa, Iowa City, USA., Close LN; Department of Neurosurgery, Carver College of Medicine, University of Iowa, Iowa City, USA., Dlouhy BJ; Department of Neurosurgery, Carver College of Medicine, University of Iowa, Iowa City, USA., Howard MA 3rd; Department of Neurosurgery, Carver College of Medicine, University of Iowa, Iowa City, USA., Kawasaki H; Department of Neurosurgery, Carver College of Medicine, University of Iowa, Iowa City, USA., Stein KM; Department of Oral and Maxillofacial Surgery, Carver College of Medicine, University of Iowa, Iowa City, USA., Potash JB; Department of Psychiatry and Behavioral Science, School of Medicine, Johns Hopkins University, Baltimore, USA., Shinozaki G; Department of Psychiatry, Carver College of Medicine, University of Iowa, Iowa City, USA.; Department of Neurosurgery, Carver College of Medicine, University of Iowa, Iowa City, USA.; Iowa Neuroscience Institute, Carver College of Medicine, University of Iowa, Iowa City, USA.; Interdisciplinary Graduate Program for Neuroscience, Carver College of Medicine, University of Iowa, Iowa City, USA.
Jazyk: angličtina
Zdroj: Psychiatry and clinical neurosciences [Psychiatry Clin Neurosci] 2019 Jun; Vol. 73 (6), pp. 323-330. Date of Electronic Publication: 2019 Mar 28.
DOI: 10.1111/pcn.12835
Abstrakt: Aim: Glucocorticoids play a major role in regulating the stress response, and an imbalance of glucocorticoids has been implicated in stress-related disorders. Within mouse models, CpGs across the genome have been shown to be differentially methylated in response to glucocorticoid treatment, and using the Infinium 27K array, it was shown that humans given synthetic glucocorticoids had DNA methylation (DNAm) changes in blood. However, further investigation of the extent to which glucocorticoids affect DNAm across a larger proportion of the genome is needed.
Methods: Buccal samples were collected before and after synthetic glucocorticoid treatment in the context of a dental procedure. This included 30 tooth extraction surgery patients who received 10 mg of dexamethasone. Genome-wide DNAm was assessed with the Infinium HumanMethylationEPIC array.
Results: Five CpGs showed genome-wide significant DNAm changes that were >10%. These differentially methylated CpGs were in or nearest the following genes: ZNF438, KLHDC10, miR-544 or CRABP1, DPH5, and WDFY2. Using previously published datasets of human blood gene expression changes following dexamethasone exposure, a significant proportion of genes with false-discovery-rate-adjusted significant CpGs were also differentially expressed. A pathway analysis of the genes with false-discovery-rate-adjusted significant CpGs revealed significant enrichment of olfactory transduction, pentose and glucuronate interconversions, ascorbate and aldarate metabolism, and steroid hormone biosynthesis pathways.
Conclusion: High-dose synthetic glucocorticoid administration in the setting of a dental procedure was significantly associated with DNAm changes within buccal samples. These findings are consistent with prior findings of an influence of glucocorticoids on DNAm in humans.
(© 2019 The Authors. Psychiatry and Clinical Neurosciences © 2019 Japanese Society of Psychiatry and Neurology.)
Databáze: MEDLINE
Externí odkaz:
Nepřihlášeným uživatelům se plný text nezobrazuje