BDNF rs6265 polymorphism methylation in Multiple Sclerosis: A possible marker of disease progression.

Autor: Nociti V; Institute of Neurology, Fondazione Policlinico Universitario A. Gemelli IRCCS-Università Cattolica del Sacro Cuore, Rome, Italy., Santoro M; IRCCS Fondazione Don Carlo Gnocchi, Milan, Italy., Quaranta D; Institute of Neurology, Fondazione Policlinico Universitario A. Gemelli IRCCS-Università Cattolica del Sacro Cuore, Rome, Italy., Losavio FA; Institute of Neurology, Fondazione Policlinico Universitario A. Gemelli IRCCS-Università Cattolica del Sacro Cuore, Rome, Italy., De Fino C; Institute of Neurology, Fondazione Policlinico Universitario A. Gemelli IRCCS-Università Cattolica del Sacro Cuore, Rome, Italy., Giordano R; Institute of Neurology, Fondazione Policlinico Universitario A. Gemelli IRCCS-Università Cattolica del Sacro Cuore, Rome, Italy., Palomba NP; Institute of Neurology, Fondazione Policlinico Universitario A. Gemelli IRCCS-Università Cattolica del Sacro Cuore, Rome, Italy., Rossini PM; Institute of Neurology, Fondazione Policlinico Universitario A. Gemelli IRCCS-Università Cattolica del Sacro Cuore, Rome, Italy., Guerini FR; IRCCS Fondazione Don Carlo Gnocchi, Milan, Italy., Clerici M; Department of Physiopathology and Transplantation, University of Milan, Milan, Italy., Caputo D; IRCCS Fondazione Don Carlo Gnocchi, Milan, Italy., Mirabella M; Institute of Neurology, Fondazione Policlinico Universitario A. Gemelli IRCCS-Università Cattolica del Sacro Cuore, Rome, Italy.
Jazyk: angličtina
Zdroj: PloS one [PLoS One] 2018 Oct 23; Vol. 13 (10), pp. e0206140. Date of Electronic Publication: 2018 Oct 23 (Print Publication: 2018).
DOI: 10.1371/journal.pone.0206140
Abstrakt: Introduction: Brain-Derived Neurotrophic Factor (BDNF) and its most common polymorphism Val66Met are known to have a role in Multiple Sclerosis (MS) pathogenesis. Evidence is accumulating that there is an involvement of DNA methylation in the regulation of BDNF expression. The aim of this study was to assess in blood samples of MS patients the correlation between the methylation status of the CpG site near BDNF-Val66Met polymorphism and the severity of the disease.
Methods: We recruited 209 MS patients that were genotyped for the BDNF Val66Met polymorphism. For each patient we quantitatively measured the methylation level of cytosine included in the exonic CpG site that can be created or abolished by the Val66Met BDNF polymorphism. Furthermore, we analyzed the clinical history of each patient and determined the time elapsed since the onset of the disease and an EDSS score of 6.0.
Results: The genetic analysis identified 122 (58.4%) subjects carrying the Val/Val genotype, 81 (38.8%) with Val/Met genotype, and 6 (2.8%) carrying the Met/Met genotype. When the endpoint of an EDSS score of 6 was taken into account by means of a survival analysis, 52 failures (i.e., reaching an EDSS score of 6) were reported. When the sample was stratified according to the percentage of the BDNF methylation, subjects falling below the median (median methylation = 81%) were at higher risk of failure (IRD = 0.016; 95%CI = 0.0050-0.0279; p = 0.004).
Conclusions: In patients with a high disease progression the hypomethylation of the BDNF gene could increase the secretion of the protective neurotrophin, so epigenetic modifications could be the organism response to limit a brain functional reserve loss. Our study suggests that the percentage of methylation of the BDNF gene could be used as a prognostic factor for disease progression toward a high disability in MS patient.
Competing Interests: The authors have declared that no competing interests exist.
Databáze: MEDLINE
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