PMID- 30352103
OWN - NLM
STAT- MEDLINE
DCOM- 20190401
LR  - 20190401
IS  - 1932-6203 (Electronic)
IS  - 1932-6203 (Linking)
VI  - 13
IP  - 10
DP  - 2018
TI  - BDNF rs6265 polymorphism methylation in Multiple Sclerosis: A possible marker of 
      disease progression.
PG  - e0206140
LID - 10.1371/journal.pone.0206140 [doi]
LID - e0206140
AB  - 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.
FAU - Nociti, Viviana
AU  - Nociti V
AD  - Institute of Neurology, Fondazione Policlinico Universitario A. Gemelli 
      IRCCS-Universita Cattolica del Sacro Cuore, Rome, Italy.
FAU - Santoro, Massimo
AU  - Santoro M
AD  - IRCCS Fondazione Don Carlo Gnocchi, Milan, Italy.
FAU - Quaranta, Davide
AU  - Quaranta D
AD  - Institute of Neurology, Fondazione Policlinico Universitario A. Gemelli 
      IRCCS-Universita Cattolica del Sacro Cuore, Rome, Italy.
FAU - Losavio, Francesco Antonio
AU  - Losavio FA
AD  - Institute of Neurology, Fondazione Policlinico Universitario A. Gemelli 
      IRCCS-Universita Cattolica del Sacro Cuore, Rome, Italy.
FAU - De Fino, Chiara
AU  - De Fino C
AD  - Institute of Neurology, Fondazione Policlinico Universitario A. Gemelli 
      IRCCS-Universita Cattolica del Sacro Cuore, Rome, Italy.
FAU - Giordano, Rocco
AU  - Giordano R
AD  - Institute of Neurology, Fondazione Policlinico Universitario A. Gemelli 
      IRCCS-Universita Cattolica del Sacro Cuore, Rome, Italy.
FAU - Palomba, Nicole Piera
AU  - Palomba NP
AD  - Institute of Neurology, Fondazione Policlinico Universitario A. Gemelli 
      IRCCS-Universita Cattolica del Sacro Cuore, Rome, Italy.
FAU - Rossini, Paolo Maria
AU  - Rossini PM
AD  - Institute of Neurology, Fondazione Policlinico Universitario A. Gemelli 
      IRCCS-Universita Cattolica del Sacro Cuore, Rome, Italy.
FAU - Guerini, Franca Rosa
AU  - Guerini FR
AD  - IRCCS Fondazione Don Carlo Gnocchi, Milan, Italy.
FAU - Clerici, Mario
AU  - Clerici M
AD  - Department of Physiopathology and Transplantation, University of Milan, Milan, 
      Italy.
FAU - Caputo, Domenico
AU  - Caputo D
AD  - IRCCS Fondazione Don Carlo Gnocchi, Milan, Italy.
FAU - Mirabella, Massimiliano
AU  - Mirabella M
AUID- ORCID: 0000-0002-7783-114X
AD  - Institute of Neurology, Fondazione Policlinico Universitario A. Gemelli 
      IRCCS-Universita Cattolica del Sacro Cuore, Rome, Italy.
LA  - eng
PT  - Journal Article
DEP - 20181023
PL  - United States
TA  - PLoS One
JT  - PloS one
JID - 101285081
RN  - 0 (Brain-Derived Neurotrophic Factor)
SB  - IM
EIN - PLoS One. 2019 Feb 21;14(2):e0212906. PMID: 30789956
MH  - Brain-Derived Neurotrophic Factor/*genetics
MH  - *DNA Methylation
MH  - Disease Progression
MH  - Female
MH  - Follow-Up Studies
MH  - Gene Frequency
MH  - Genetic Predisposition to Disease/*genetics
MH  - Genotype
MH  - Humans
MH  - Male
MH  - Multiple Sclerosis/*genetics/pathology
MH  - *Polymorphism, Single Nucleotide
MH  - Prognosis
MH  - Survival Analysis
PMC - PMC6198951
COIS- The authors have declared that no competing interests exist.
EDAT- 2018/10/24 06:00
MHDA- 2019/04/02 06:00
PMCR- 2018/10/23
CRDT- 2018/10/24 06:00
PHST- 2018/05/27 00:00 [received]
PHST- 2018/10/08 00:00 [accepted]
PHST- 2018/10/24 06:00 [entrez]
PHST- 2018/10/24 06:00 [pubmed]
PHST- 2019/04/02 06:00 [medline]
PHST- 2018/10/23 00:00 [pmc-release]
AID - PONE-D-18-15886 [pii]
AID - 10.1371/journal.pone.0206140 [doi]
PST - epublish
SO  - PLoS One. 2018 Oct 23;13(10):e0206140. doi: 10.1371/journal.pone.0206140. 
      eCollection 2018.