Abstract
SU60GENOME-WIDE DNA METHYLATION INVESTIGATION OF SYNTHETIC GLUCOCORTICOID EXPOSURE WITHIN HUMAN BUCCAL SAMPLES
European neuropsychopharmacology, Vol.29(Supplement 4), pp.S1299-S1300
2019
DOI: 10.1016/j.euroneuro.2018.08.424
Abstract
abstract only
Background: 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 oral surgery. This included 30 minor tooth extraction surgery patients who received 10 mg of dexamethasone. Genome-wide DNAm was assessed with the Infinium HumanMethylationEPIC array. Data were processed and analyzed with the R packages Minfi and RnBeads.
Results: Five CpGs showed genome-wide significant change in DNAm that was >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 FDR-adjusted significant CpGs were also differentially expressed. A pathway analysis of the genes with FDR-adjusted significant CpGs revealed significant enrichment of olfactory transduction, pentose and glucuronate interconversions, ascorbate and aldarate metabolism, and steroid hormone biosynthesis pathways. In a replication cohort of patients with treatment refractory epilepsy, brain, blood, buccal, and saliva samples were obtained before and after dexamethasone treatment. A portion of the FDR-adjusted significant CpGs in the discovery cohort were also nominally significant in the replication cohort (13 CpGs in blood, 5 in buccal tissue, 58 in saliva, and 6 in brain), and one of the CpGs that replicated in saliva also withstood correction for multiple testing.
Discussion: In conclusion, high-dose synthetic glucocorticoid administration in the setting of oral surgery 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.
Details
- Title: Subtitle
- SU60GENOME-WIDE DNA METHYLATION INVESTIGATION OF SYNTHETIC GLUCOCORTICOID EXPOSURE WITHIN HUMAN BUCCAL SAMPLES
- Creators
- Patricia Braun - University of Iowa Carver College of MedicineBenjamin Hing - University of Iowa Carver College of MedicineMai Tanaka-Sahker - University of Iowa Carver College of MedicineAubrey Chan - University of Iowa Carver College of MedicineYasunori Nagahama - University of Iowa Carver College of MedicineLindsey Gaul - University of Iowa Carver College of MedicineJonathan Heinzman - University of Iowa Carver College of MedicineKumi Yuki - University of Iowa Carver College of MedicineLiesl Close - University of Iowa Carver College of MedicineBrian Dlouhy - University of Iowa Carver College of MedicineHiroto Kawasaki - University of Iowa Carver College of MedicineKyle Stein - University of Iowa Carver College of MedicineJames Potash - Johns HopkinsGen Shinozaki - University of Iowa Carver College of Medicine
- Resource Type
- Abstract
- Publication Details
- European neuropsychopharmacology, Vol.29(Supplement 4), pp.S1299-S1300
- DOI
- 10.1016/j.euroneuro.2018.08.424
- ISSN
- 0924-977X
- eISSN
- 1873-7862
- Publisher
- Elsevier B.V
- Language
- English
- Date published
- 2019
- Academic Unit
- Molecular Physiology and Biophysics; Psychiatry; Iowa Neuroscience Institute; Family and Community Medicine; Anesthesia; Oral and Maxillofacial Surgery; Neurosurgery
- Record Identifier
- 9984072062702771
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