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Repetitive element hypermethylation in multiple sclerosis patients.

K Y Neven1,2, M Piola3, L Angelici1

  • 1Department of Clinical Sciences and Community Health, EPIGET - Epidemiology, Epigenetics and Toxicology Lab, Università degli Studi di Milano, Milan, Italy.

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|June 19, 2016
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Summary

Multiple sclerosis (MS) patients show hypermethylation in repetitive elements like Alu and LINE-1 compared to controls. These epigenetic changes may serve as markers for MS disability, impacting disease understanding.

Keywords:
DNA methylationEpigeneticsExpanded disability status scaleHypermethylationMultiple sclerosisRepetitive elements

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Area of Science:

  • Neuroscience
  • Genetics
  • Epigenetics

Background:

  • Multiple sclerosis (MS) is a central nervous system disorder with unknown etiology.
  • Growing evidence suggests DNA methylation alterations contribute to inflammatory and neurodegenerative diseases, potentially playing a role in MS pathogenesis.
  • Repetitive elements (Alu, LINE-1, SAT-α) are established global DNA methylation estimators.

Purpose of the Study:

  • To investigate differences in Alu, LINE-1, and SAT-α methylation levels between MS patients and healthy controls.
  • To evaluate the role of these repetitive elements as potential biomarkers of disability in multiple sclerosis.
  • To explore the association between DNA methylation patterns and the Expanded Disability Status Scale (EDSS) in MS.

Main Methods:

  • Blood samples were collected from 51 MS patients and 137 age, gender, and smoking-matched healthy volunteers.
  • DNA methylation levels of repetitive elements (Alu, LINE-1, SAT-α) were assessed using bisulfite-PCR-pyrosequencing.
  • Clinical data, including medical history and neurological examination (EDSS), were collected for all participants.

Main Results:

  • All investigated repetitive elements (Alu, LINE-1, SAT-α) were found to be hypermethylated in MS patients compared to healthy controls.
  • Lower LINE-1 methylation levels correlated with lower EDSS scores ('EDSS = 1.0' and '1.5 ≤ EDSS ≤ 2.5') compared to higher EDSS scores (>3).
  • Alu methylation levels were higher in MS patients with lower EDSS scores ('EDSS = 1.0' and '1.5 ≤ EDSS ≤ 2.5') compared to those with higher EDSS scores.

Conclusions:

  • MS patients exhibit global hypermethylation in repetitive elements compared to healthy individuals.
  • Alu and LINE-1 methylation levels are associated with the degree of disability in multiple sclerosis, as measured by the EDSS.
  • Further epigenetic research is warranted to elucidate the complex pathogenetic mechanisms of MS and the role of DNA methylation.