<p><em>MTHFR</em>‑folate axis as a modulator of the epigenetic landscape in autoimmune diseases (Review)</p>

Navarro‑Rodríguez,Pablo Michael; Bajeca‑Serrano,Ramón Francisco; Turrubiates‑Hernández,Francisco Javier; Ceja‑Gálvez,Hazael Ramiro; Hernández‑Bello,Jorge; Hernández‑Ramírez,Cristian Oswaldo; Ramírez‑de Los Santos,Saúl; Muñoz‑Valle,José Francisco

doi:10.3892/ijmm.2026.5741

March-2026 Volume 57 Issue 3

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March-2026 Volume 57 Issue 3

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Review Open Access

MTHFR‑folate axis as a modulator of the epigenetic landscape in autoimmune diseases (Review)

Authors:
- Pablo Michael Navarro‑Rodríguez
- Ramón Francisco Bajeca‑Serrano
- Francisco Javier Turrubiates‑Hernández
- Hazael Ramiro Ceja‑Gálvez
- Jorge Hernández‑Bello
- Cristian Oswaldo Hernández‑Ramírez
- Saúl Ramírez‑de Los Santos
- José Francisco Muñoz‑Valle
View Affiliations / Copyright

Affiliations: Department of Molecular Biology and Genomics, University Center of Health Sciences, University of Guadalajara, Guadalajara, Jalisco 44340, Mexico, Department of Clinical Medicine, Institute of Research in Biomedical Sciences, University Center of Health Sciences, University of Guadalajara, Guadalajara, Jalisco 44340, Mexico

Copyright: © Navarro‑Rodríguez et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
Article Number: 70
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Published online on: January 22, 2026

https://doi.org/10.3892/ijmm.2026.5741
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Abstract

The one‑carbon metabolism pathway, regulated by the methylenetetrahydrofolate reductase (MTHFR) enzyme, represents a key nexus where genetic predisposition and nutrient status converge to shape the epigenetic landscape of autoimmune diseases. The objective of the present review is to synthesize evidence of how the MTHFR‑folate axis drives epigenomic patterns in these conditions. One of the main diseases involved is rheumatoid arthritis, where drug‑naïve patients show T‑cell and synovial hypomethylation with cytokine‑driven DNMT suppression, a process aggravated by reduced folate availability and MTHFR polymorphisms that constrain S‑adenosylmethionine supply. Similarly, in systemic lupus erythematosus, CD4⁺ T cells exhibit global hypomethylation with an interferon‑skewed signature (such as IFI44L), associated with impaired MTHFR activity and a folate‑dependent SAM:SAH imbalance that further diminishes DNMT function. Finally, in celiac disease, intestinal differential methylation, including LINE‑1 hypomethylation, is observed, driven by gluten‑induced villous atrophy and folate malabsorption. Overall, impaired one‑carbon metabolism and MTHFR‑dependent methylation capacity may be key determinants of epigenomic dysfunction underlying autoimmune disease and its clinical severity.17

Journals

International Journal of Molecular Medicine

International Journal of Oncology

Molecular Medicine Reports

Oncology Reports

Experimental and Therapeutic Medicine

Oncology Letters

Biomedical Reports

Molecular and Clinical Oncology

World Academy of Sciences Journal

International Journal of Functional Nutrition

International Journal of Epigenetics

Medicine International

MTHFR‑folate axis as a modulator of the epigenetic landscape in autoimmune diseases (Review)

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Abstract

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