Repetitive element hypermethylation in multiple sclerosis patients.
Multiple sclerosis (MS) is a complex disorder of the central nervous system whose cause is currently unknown. Evidence is increasing that DNA methylation alterations could be involved in inflammatory and neurodegenerative diseases and could contribute to MS pathogenesis. Repetitive elements Alu, LINE-1 and SAT-α, are widely known as estimators of global DNA methylation. We investigated Alu, LINE-1 and SAT-α methylation levels to evaluate their difference in a case-control setup and their role as a marker of disability.



We obtained blood samples from 51 MS patients and 137 healthy volunteers matched by gender, age and smoking. Methylation was assessed using bisulfite-PCR-pyrosequencing. For all participants, medical history, physical and neurological examinations and screening laboratory tests were collected. All repetitive elements were hypermethylated in MS patients compared to healthy controls. A lower Expanded Disability Status Scale (EDSS) score was associated with a lower levels of LINE-1 methylation for 'EDSS = 1.0' and '1.5 ≤ EDSS ≤ 2.5' compared to an EDSS higher than 3, while Alu was associated with a higher level of methylation in these groups: 'EDSS = 1.0' and '1.5 ≤ EDSS ≤ 2.5'.



MS patients exhibit an hypermethylation in repetitive elements compared to healthy controls. Alu and LINE-1 were associated with degree of EDSS score. Forthcoming studies focusing on epigenetics and the multifactorial pathogenetic mechanism of MS could elucidate these links further.
Department of Clinical Sciences and Community Health, EPIGET - Epidemiology, Epigenetics and Toxicology Lab, Università degli Studi di Milano, Milan, Italy.|Centre for Environmental Sciences, Hasselt University, Diepenbeek, Belgium.
K Y
KY
Neven
Neurology Unit, Saronno ASST Valle Olona Hospital, Saronno, Italy.
M
M
Piola
Department of Clinical Sciences and Community Health, EPIGET - Epidemiology, Epigenetics and Toxicology Lab, Università degli Studi di Milano, Milan, Italy.
L
L
Angelici
Department of Preventive Medicine, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Epidemiology Unit, Milan, Italy.
F
F
Cortini
Department of Pathophysiology and Transplantation, Dino Ferrari Centre, Università degli Studi di Milano and Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy.
C
C
Fenoglio
Department of Pathophysiology and Transplantation, Dino Ferrari Centre, Università degli Studi di Milano and Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy.
D
D
Galimberti
Department of Clinical Sciences and Community Health, EPIGET - Epidemiology, Epigenetics and Toxicology Lab, Università degli Studi di Milano, Milan, Italy.|Department of Preventive Medicine, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Epidemiology Unit, Milan, Italy.
A C
AC
Pesatori
Department of Pathophysiology and Transplantation, Dino Ferrari Centre, Università degli Studi di Milano and Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy.
E
E
Scarpini
Department of Clinical Sciences and Community Health, EPIGET - Epidemiology, Epigenetics and Toxicology Lab, Università degli Studi di Milano, Milan, Italy. valentina.bollati@unimi.it.|Department of Preventive Medicine, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Epidemiology Unit, Milan, Italy. valentina.bollati@unimi.it.|Department of Clinical Sciences and Community Health, Valentina Bollati, Università degli Studi di Milano, Via San Barnaba 8, 20122, Milan, Italy. valentina.bollati@unimi.it.
V
V
Bollati
D000328:Adult; D020087:Alu Elements; D019175:DNA Methylation; D005260:Female; D006801:Humans; D020084:Long Interspersed Nucleotide Elements; D008297:Male; D009103:Multiple Sclerosis / Q000235:genetics*; D012091:Repetitive Sequences, Nucleic Acid
DNA methylation; Epigenetics; Expanded disability status scale; Hypermethylation; Multiple sclerosis; Repetitive elements