Epigenetic Alterations and an Increased Frequency of Micronuclei in Women with Fibromyalgia

Abstract

Fibromyalgia (FM), characterized by chronic widespread pain, fatigue, and cognitive/mood disturbances, leads to reduced workplace productivity and increased healthcare expenses. To determine if acquired epigenetic/genetic changes are associated with FM, we compared the frequency of spontaneously occurring micronuclei (MN) and genome-wide methylation patterns in women with FM (n = 10) to those seen in comparably aged healthy controls (n = 42 (MN); n = 8 (methylation)). The mean (sd) MN frequency of women with FM (51.4 (21.9)) was significantly higher than that of controls (15.8 (8.5)) (χ 2 = 45.552; df = 1; P = 1.49 × 10−11). Significant differences (n = 69 sites) in methylation patterns were observed between cases and controls considering a 5% false discovery rate. The majority of differentially methylated (DM) sites (91%) were attributable to increased values in the women with FM. The DM sites included significant biological clusters involved in neuron differentiation/nervous system development, skeletal/organ system development, and chromatin compaction. Genes associated with DM sites whose function has particular relevance to FM included BDNF, NAT15, HDAC4, PRKCA, RTN1, and PRKG1. Results support the need for future research to further examine the potential role of epigenetic and acquired chromosomal alterations as a possible biological mechanism underlying FM.

Investigation of genetic variants in ubiquitin enzyme genes involved in the modulation of neurodevelopmental processes: a role in schizophrenia susceptibility?

“…Differential epigenetic gene regulation in relation to traumatic childhood experiences has only ever been reported for one ubiquitin E3 ligase (Mahogunin Ring Finger 1 or MGRN1) in women with fibromyalgia who had experienced traumatic childhood events (Menzies et al, 2013). This suggests that adverse childhood experiences are able to induce genetic and epigenetic variations in ubiquitin protein genes responding to stressful conditions such as Ring Type E3 ubiquitin ligase and F-box proteins (Hermand, 2006;Hua and Vierstra, 2011).…”

Fibromyalgia: A Critical and Comprehensive Review

“…Therefore, some of the discrepant findings concerning the association of this SNP with FMS (see Table 5) may arise from differential methylation and gene expression in carriers of the C allele [478]. In a pilot study, it was recently shown that the genome-wide methylation pattern differed significantly between women with FMS and healthy controls [479]. Of 69 differentially methylated sites, 63 showed a higher degree of methylation in FMS patients.…”

The Correlation Between Depression and Hopelessness Scores and Cytological Features of Exfoliated Buccal Cells in Females

“…The frequency of MN has been revealed to be increased in patients affected by neurodegenerative disorders, such as Alzheimer's and Parkinson's disease, and psychiatric disorders, such as anorexia nervosa and bulimia nervosa (9,15). It has been shown that the number of MN in females with fibromyalgia was significantly higher than that of controls (16). Fibromyalgia is a multi-factorial disease and psychiatric disorders seem to play a crucial role in its pathophysiology (17).…”