# LINE-1 Methylation Status in Multiple Sclerosis Patients Is Associated with Changes in Folate Metabolism

**Authors:** E. A. Tsymbalova, E. A. Chernyavskaya, G. N. Bisaga, A. Y. Polushin, E. I. Lopatina, I. N. Abdurasulova, V. I. Lioudyno

PMC · DOI: 10.32607/actanaturae.27579 · Acta Naturae · 2025-07-01

## TL;DR

This study finds that methylation levels in MS patients are linked to folate metabolism and disease progression.

## Contribution

The study reveals a novel association between LINE-1 methylation, folate metabolism, and MS progression.

## Key findings

- LINE-1 methylation levels decrease with age in healthy individuals.
- MS patients show higher LINE-1 methylation in progressive forms compared to remitting types.
- Methylation variations correlate with homocysteine, vitamin B9, and MTHFR C677T genotype.

## Abstract

The disruption of epigenetic regulation and the development of abnormal DNA
methylation patterns are crucial steps in the pathogenesis of neurodegenerative
diseases. Methylation alterations in multiple sclerosis (MS) patients may
contribute to the dysregulation of gene expression linked to the regulation of
inflammation, myelin production, and the preservation of the integrity of the
myelin sheath. The possibility that epigenetic alterations could be reversed
provides a rationale for studying their mechanisms. In this study, we evaluated
the methylation status of LINE-1 retrotransposons in the peripheral blood cells
of patients with MS and healthy controls. In healthy individuals, LINE-1
methylation levels were observed to decrease with advancing age. MS patients
exhibited a positive correlation between LINE-1 methylation and MS duration.
The study indicates that the level of LINE-1 methylation is notably higher in
progressive MS compared to the remitting type. LINE-1 methylation variations in
MS patients were observed to be associated with the serum levels of
homocysteine and vitamin B9, and dependent on the genotype for the C677T
polymorphism of the MTHFR gene as well. The data obtained
point to the contribution of the C677T polymorphism to the appearance of
epigenetic disorders in MS development and suggest that hypermethylation may be
mediated by disruptions in the folate metabolism that accompany MS.

## Linked entities

- **Genes:** MTHFR (methylenetetrahydrofolate reductase) [NCBI Gene 4524]
- **Chemicals:** homocysteine (PubChem CID 778), vitamin B9 (PubChem CID 135398658)
- **Diseases:** multiple sclerosis (MONDO:0005301)

## Full-text entities

- **Genes:** MTHFR (methylenetetrahydrofolate reductase) [NCBI Gene 4524]
- **Diseases:** neurodegenerative diseases (MESH:D019636), inflammation (MESH:D007249), MS (MESH:D009103)
- **Chemicals:** Folate (MESH:D005492), homocysteine (MESH:D006710)
- **Species:** Homo sapiens (human, species) [taxon 9606]
- **Mutations:** C677T

## Full text

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## Figures

6 figures with captions in the complete paper: https://tomesphere.com/paper/PMC12536986/full.md

## References

39 references — full list in the complete paper: https://tomesphere.com/paper/PMC12536986/full.md

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Source: https://tomesphere.com/paper/PMC12536986