DNA Methylation and BDNF Expression account for symptoms and widespread hyperalgesia in patients with Chronic Fatigue Syndrome and Fibromyalgia, by Andrea Polli, Manosij Ghosh, Jelena Bakusic, Kelly Ickmans, Dora Monteyne, Brigitte Velkeniers, Bram Bekaert, Lode Godderis, Jo Nijs in Arthritis Rheumatol. 2020 Jun 20 [doi: 10.1002/art.41405]
Epigenetics of neurotrophic factors holds the potential to unravel the mechanisms underlying the pathophysiology of complex conditions such as chronic fatigue syndrome (CFS). This study explored the role of brain-derived neurotrophic factor (BDNF) genetics, epigenetics, and protein expression in patients with both CFS and comorbid fibromyalgia (CFS/FM).
A repeated-measures study in 54 participants (28 patients with CFS/FM and 26 matched healthy controls) was conducted.
Participants underwent a comprehensive assessment, including questionnaires, sensory testing, and blood withdrawal. BDNF protein level was measured in serum (sBDNF) using ELISA, while polymorphism and DNA methylation were measured in blood, using pyrosequencing technology. To assess temporal stability of the measures, participants underwent the same assessment twice within four days.
Repeated-measures mixed linear models were performed for between-group analysis. sBNDF was higher in patients with CFS/FM (F=15.703; mean difference: 3.31 ng/ml, 95% C.I. 1.65 to 4.96; p=.001), whereas BDNF DNA methylation was lower in Exon IX (F=9.312; mean difference -2.38%, C.I. -3.93 to -0.83; p=.003). BDNF DNA methylation was mediated by the Val66Met (rs6265) polymorphism. Lower methylation in the same region predicted higher sBDNF (F=4.910, t= -2.216, p=.029, 95% C.I. = -.712 to -.039) which in turn predicted participants’ symptoms (F=14.410, t= 3.796, 95% C.I.= 1.79 to 5.71, p=.001) and widespread hyperalgesia (F=4.147, t= 2.036, 95% C.I.= .01 to .08, p=.044).
sBDNF is higher in patients with CFS/FM and BDNF methylation in exon IX accounts for regulating protein expression. Altered BDNF might represent a key mechanism explaining CFS/FM pathophysiology.