Chronic Fatigue Syndrome and DNA Hypomethylation of the Glucocorticoid Receptor Gene Promoter 1F Region

Associations With HPA Axis Hypofunction and Childhood Trauma

Bibliographic Data

ID19307172
AuthorsElise Vangeel (Antwerp University Hospital, corresponding author), Filip Van Den Eede (0000-0002-1942-1601), Titia Hompes (0000-0002-6206-0389), Benedetta Izzi (0000-0002-3649-7931), Jurgen Del Favero, Jurgen Del‐Favero (0000-0002-7427-7489), Greta Moorkens (0000-0002-9381-944X), Diether Lambrechts (0000-0002-3429-302X), Kathleen Freson (0000-0002-4381-2442), Stephan Claes (0000-0002-1175-492X)
Year2015
Volume77
Issue8
Pages853-862
Publication date2015-10-01
Open AccessNo
TypeARTICLE
VenuePsychosomatic Medicine (JOURNAL)
Journal identifiersISSN: 0033-3174 • E-ISSN: 1534-7796
PublisherOvid Technologies (Wolters Kluwer Health) (PUBLISHER)
DOI10.1097/psy.0000000000000224
PMID26230484
OpenAlexW1136951987
LanguageEN
Citations received4
References cited42

OBJECTIVES: Chronic fatigue syndrome (CFS) has been associated with hypothalamic-pituitary-adrenal axis hypofunction and enhanced glucocorticoid receptor (GR) sensitivity. In addition, childhood trauma is considered a major risk factor for the syndrome. This study examines DNA methylation of the GR gene (NR3C1) in CFS and associations with childhood sexual and physical trauma. METHODS: Quantification of DNA methylation within the 1F promoter region of NR3C1 was performed in 76 female patients (46 with no/mild and 30 with moderate/severe childhood trauma) and 19 healthy controls by using Sequenom EpiTYPER. Further, we examined the association of NR3C1-1F promoter methylation with the outcomes of the low-dose (0.5 mg) dexamethasone/corticotropin-releasing factor test in a subset of the study population. Mann-Whitney U tests and Spearman correlations were used for statistical analyses. RESULTS: Overall NR3C1-1F DNA methylation was lower in patients with CFS than in controls. After cytosine guanine dinucleotide (CpG)-specific analysis, CpG_1.5 remained significant after Bonferroni correction (adjusted p = .0014). Within the CFS group, overall methylation (ρ = 0.477, p = .016) and selective CpG units (CpG_1.5: ρ = 0.538, p = .007; CpG_12.13: ρ = 0.448, p = .025) were positively correlated with salivary cortisol after dexamethasone administration. There was no significant difference in NR3C1-1F methylation between traumatized and nontraumatized patients. CONCLUSIONS: We found evidence of NR3C1 promoter hypomethylation in female patients with CFS and the functional relevance of these differences was consistent with the hypothalamic-pituitary-adrenalaxis hypofunction hypothesis (GR hypersuppression). However, we found no evidence of an additional effect of childhood trauma on CFS via alterations in NR3C1 methylation

Biology · CpG site · DNA methylation · Gene · Gene expression · Glucocorticoid · Glucocorticoid receptor · Methylation · Promoter · Adrenal Hormones and Disorders · Endocrinology · Fibromyalgia and Chronic Fatigue Syndrome Research · Genetics · Internal Medicine · Medicine · Stress Responses and Cortisol

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