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LINE-1 Methylation Status in Multiple Sclerosis Patients Is Associated with Changes in Folate Metabolism
E A Tsymbalova1, E A Chernyavskaya1, G N Bisaga2
1FSBSI "Institute of Experimental medicine", Saint Petersburg, 197022 Russia.
Acta Naturae
|October 22, 2025
Summary
Epigenetic changes, specifically LINE-1 methylation, are altered in multiple sclerosis (MS) patients, correlating with disease duration and severity. These variations are linked to folate metabolism and MTHFR gene variants, suggesting potential therapeutic targets.
Area of Science:
- Neuroscience
- Epigenetics
- Genetics
Background:
- Epigenetic dysregulation, including abnormal DNA methylation, is implicated in neurodegenerative diseases like multiple sclerosis (MS).
- Alterations in methylation patterns in MS may affect gene expression related to inflammation and myelin integrity.
- The potential reversibility of epigenetic changes warrants investigation into their mechanisms.
Purpose of the Study:
- To investigate LINE-1 retrotransposon methylation status in peripheral blood cells of MS patients and healthy controls.
- To explore the relationship between LINE-1 methylation, MS duration, disease type, and relevant biochemical factors.
Main Methods:
- Analysis of LINE-1 retrotransposon methylation levels in peripheral blood cells.
- Comparison between multiple sclerosis patients and healthy individuals.
- Correlation analysis with clinical data (MS duration, type) and biochemical markers (homocysteine, vitamin B9, MTHFR genotype).
Main Results:
- LINE-1 methylation decreased with age in healthy individuals.
- MS patients showed a positive correlation between LINE-1 methylation and MS duration.
- Progressive MS exhibited higher LINE-1 methylation than remitting MS.
- LINE-1 methylation variations were associated with homocysteine, vitamin B9 levels, and MTHFR C677T genotype.
Conclusions:
- LINE-1 methylation patterns are altered in MS and associated with disease progression.
- The MTHFR C677T polymorphism contributes to epigenetic alterations in MS.
- Folate metabolism disruptions may mediate hypermethylation in MS pathogenesis.

