Background and aims. Fibromyalgia (FM) is a pathological condition characterized by chronic widespread pain and comorbid symptoms. Its multifactorial nature makes complex the diagnosis, the identification of underlying etiological mechanisms and effective therapies. Epigenetics, reflecting the influence of environmental co-factors, might reveal biomarkers for both basic research and clinical practice. This pilot study aims to investigate DNA methylation in genome regions of eight FM women compared to their healthy sisters.
Methods. Methylation status was tested in leukocytes’ DNA by bisulfite sequencing (Illumina) of 240.134kbp (Agilent SureSelectXTTarget Enrichment System), including CpGs in promoters of genes previously found associated with FM or related symptoms. Chronic pain, sleep problems and depression were respectively explored using FIQ (Fibromyalgia Impact Questionnaire), WPI (Widespread Index), Symptom Severity Scale (SS), Visual Analogue Scale (VAS), PSQI (Pittsburgh Sleep Quality Index) and BDI (Beck Depression Inventory).
Results. Two regions related to GRM2 and DRD3 genes were found differentially methylated comparing eight FM women and their sisters. Twenty-four differentially methylated cytosines were identified with p-value<0.05, ten of which related to GRM2 gene. 
Conclusion. This is the first study profiling DNA methylation at single-base resolution in targeted regions of FM women and their sisters. Given the small sample size and the high genome coverage, more in-depth analyses on a larger number of patients need to investigate the regions identified. In light of the suffering of FM patients and the huge medical/social costs associated, it’s worth to clarify if epigenetics might reveal new perspectives.

TARGETED SINGLE BASE RESOLUTION ANALYSIS OF DNA METHYLATION IN FIBROMYALGIA WOMEN AND THEIR HEALTHY SISTERS