Andrea Polli1, Manosij Ghosh2, Jelena Bakusic3, Kelly Ickmans4, Dora Monteyne5, Brigitte Velkeniers5, Bram Bekaert6, Lode Godderis7, Jo Nijs8. 1. Vrije Universiteit Brussel, Brussels, Belgium, Katholieke Universiteit Leuven, Leuven, Belgium, and Scientific Research Foundation, Flanders, Belgium. 2. Katholieke Universiteit Leuven, Leuven, Belgium, and Scientific Research Foundation, Flanders, Belgium. 3. Katholieke Universiteit Leuven, Leuven, Belgium. 4. Vrije Universiteit Brussel and University Hospital Brussels, Brussels, Belgium, and Scientific Research Foundation, Flanders, Belgium. 5. University Hospital Brussels, Brussels, Belgium. 6. University Hospitals Leuven, and Katholieke Universiteit Leuven, Leuven, Belgium. 7. Katholieke Universiteit Leuven, Leuven, Belgium, and External Service for Prevention and Protection at Work, IDEWE, Heverlee, Belgium. 8. Vrije Universiteit Brussel, Brussels, Belgium, and University Hospital Brussels, Brussels, Belgium.
Abstract
OBJECTIVE: The 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 was undertaken to explore the role of brain-derived neurotrophic factor (BDNF) genetics, epigenetics, and protein expression in patients with both CFS and comorbid fibromyalgia (CFS/FM). METHODS: A repeated-measures study was conducted in 54 participants (28 patients with CFS/FM and 26 matched healthy controls). Participants underwent a comprehensive assessment, including questionnaires, sensory testing, and blood withdrawal. Serum BDNF (sBDNF) protein levels were measured using enzyme-linked immunosorbent assay, while polymorphism and DNA methylation were measured in blood using pyrosequencing technology. To assess the temporal stability of the measures, participants underwent the same assessment twice within 4 days. RESULTS: Repeated-measures mixed linear models were used for between-group analysis, with mean differences and 95% confidence intervals (95% CIs) shown. Compared to controls, serum BNDF was higher in patients with CFS/FM (F = 15.703; mean difference 3.31 ng/ml [95% CI 1.65, 4.96]; P = 0.001), whereas BDNF DNA methylation in exon 9 was lower (F = 7.543; mean difference -2.16% [95% CI -3.93, -0.83]; P = 0.007). BDNF DNA methylation was mediated by the Val66Met (rs6265) polymorphism. Lower methylation in the same region predicted higher sBDNF levels (F = 7.137, β = -0.408 [95% CI -0.711, -0.105]; P = 0.009), which in turn predicted participants' symptoms (F = 14.410, β = 3.747 [95% CI 1.79, 5.71]; P = 0.001) and widespread hyperalgesia (F = 4.147, β = 0.04 [95% CI 0.01, 0.08]; P = 0.044). CONCLUSION: Our findings indicate that sBDNF levels are elevated in patients with CFS/FM and that BDNF methylation in exon 9 accounts for the regulation of protein expression. Altered BDNF levels might represent a key mechanism explaining CFS/FM pathophysiology.
OBJECTIVE: The 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 was undertaken to explore the role of brain-derived neurotrophic factor (BDNF) genetics, epigenetics, and protein expression in patients with both CFS and comorbid fibromyalgia (CFS/FM). METHODS: A repeated-measures study was conducted in 54 participants (28 patients with CFS/FM and 26 matched healthy controls). Participants underwent a comprehensive assessment, including questionnaires, sensory testing, and blood withdrawal. Serum BDNF (sBDNF) protein levels were measured using enzyme-linked immunosorbent assay, while polymorphism and DNA methylation were measured in blood using pyrosequencing technology. To assess the temporal stability of the measures, participants underwent the same assessment twice within 4 days. RESULTS: Repeated-measures mixed linear models were used for between-group analysis, with mean differences and 95% confidence intervals (95% CIs) shown. Compared to controls, serum BNDF was higher in patients with CFS/FM (F = 15.703; mean difference 3.31 ng/ml [95% CI 1.65, 4.96]; P = 0.001), whereas BDNF DNA methylation in exon 9 was lower (F = 7.543; mean difference -2.16% [95% CI -3.93, -0.83]; P = 0.007). BDNF DNA methylation was mediated by the Val66Met (rs6265) polymorphism. Lower methylation in the same region predicted higher sBDNF levels (F = 7.137, β = -0.408 [95% CI -0.711, -0.105]; P = 0.009), which in turn predicted participants' symptoms (F = 14.410, β = 3.747 [95% CI 1.79, 5.71]; P = 0.001) and widespread hyperalgesia (F = 4.147, β = 0.04 [95% CI 0.01, 0.08]; P = 0.044). CONCLUSION: Our findings indicate that sBDNF levels are elevated in patients with CFS/FM and that BDNF methylation in exon 9 accounts for the regulation of protein expression. Altered BDNF levels might represent a key mechanism explaining CFS/FM pathophysiology.
Authors: Bernard X W Liew; Juan Antonio Valera-Calero; Umut Varol; Jo Nijs; Lars Arendt-Nielsen; Gustavo Plaza-Manzano; César Fernández-de-Las-Peñas Journal: Biomedicines Date: 2022-05-20
Authors: Fernando Estévez-López; Diego F Salazar-Tortosa; Daniel Camiletti-Moirón; Blanca Gavilán-Carrera; Virginia A Aparicio; Pedro Acosta-Manzano; Víctor Segura-Jiménez; Inmaculada C Álvarez-Gallardo; Ana Carbonell-Baeza; Diego Munguía-Izquierdo; Rinie Geenen; Eliana Lacerda; Manuel Delgado-Fernández; Luis J Martínez-González; Jonatan R Ruiz; María J Álvarez-Cubero Journal: J Clin Med Date: 2021-04-28 Impact factor: 4.241