06 - EPIGENETICS OF THE BRAIN-DERIVED NEUROTROPHIC FACTOR (BDNF) GENE IN PEOPLE WITH FIBROMYALGIA AND CHRONIC FATIGUE SYNDROME (FM/CFS): AN EXPLORATIVE STUDY

Background. Understanding FM/CFS from an epigenetics viewpoint might provide insight on its pathophysiology. It is hypothesised that BDNF level is higher and DNA methylation of the BDNF gene is lower in people with FM/CFS, when compared to healthy controls. Methods. We designed a cross-sectional design and enrolled 54 subjects (28 patients with CFS/ME and 26 matched healthy controls). Subjects underwent a comprehensive assessment, including clinical questionnaires, pain thresholds, and measures of BDNF protein level and gene methylation from blood. To assess temporal stability of protein levels and gene methylation, subjects underwent the same assessment twice within four days. BDNF protein level was measured using ELISA, and BDNF methylation using Pyrosequencing technology in 4 different regions (Promoter I, exon III, promoter IV, and in the coding regions, in exon IX). Results. Repeated-measures mixed models were performed for between-group analysis, so to control for time and within-group variability of the measures. BDNF protein levels were significantly higher in people with CFS/ME in both assessments (F=11.013, p=.002). On average, BNDF concentration in serum was 17.23 (4.45) ng/ml in patients, and 14.03 (3.89) ng/ml in healthy subjects. Repeated-measures mixed linear model showed that BDNF gene is hypo-methylated in promoter IX in people with FM/CFS (F=4.987; p=.03) and that lower methylation at the BDNF promoter IX is associated with higher protein expression (F=4.910, t= –2.216, p=.029, 95% C.I. = –.712 to –. 039). Discussion. BDNF protein levels is stably higher in people with FM/CFS and BDNF methylation of the coding region in exon IX might play a role in regulating protein expression.