# Global Leukocyte DNA Methylation Is Associated with Dietary Methyl-Donor Intake and Cardiometabolic Risk in Rheumatoid Arthritis and Control Subjects

**Authors:** Gerardo A. Macias, Bertha Campos-López, Karen Pesqueda-Cendejas, Paulina E. Mora-García, Eneida Turiján-Espinoza, Juan M. Vargas-Morales, Isela Parra-Rojas, Ulises De la Cruz-Mosso

PMC · DOI: 10.3390/ijms27031578 · International Journal of Molecular Sciences · 2026-02-05

## TL;DR

This study found that people with rheumatoid arthritis have lower DNA methylation levels, which are linked to diet and heart disease risk factors.

## Contribution

The study reveals a novel link between dietary methyl-donor intake, DNA methylation, and cardiometabolic risk in rheumatoid arthritis patients and controls.

## Key findings

- RA patients had significantly lower global DNA methylation levels compared to controls.
- Lower DNA methylation was associated with lower methionine intake and worse cardiometabolic profiles.
- DNA methylation levels remained lower in RA patients even after adjusting for age and BMI.

## Abstract

In rheumatoid arthritis (RA), altered DNA methylation patterns could be associated with pro-inflammatory, immune, and metabolic risk profiles. Notably, DNA methylation is dynamically regulated by the interplay of multiple factors, including diet, cardiometabolic status, and aging. Therefore, this study aimed to assess the associations between global leukocyte DNA methylation, dietary methyl-donor intake, and cardiometabolic risk in RA and control subjects (CS). A cross-sectional study was conducted with 123 female RA patients classified by the 2010 ACR-EULAR criteria, and 130 female CS. Leukocyte DNA methylation status was assessed with the 5-mC DNA ELISA Kit. RA patients exhibited significantly lower global DNA methylation levels than those with CS. RA status was independently associated with lower DNA methylation levels after adjustment for age and body mass index. Similarly, in both study groups methionine intake showed an independent inverse association with global DNA methylation across adjusted models and lower methylation levels were consistently associated with an unfavorable cardiometabolic profile, characterized by increased adverse adiposity- and lipid-related indexes. In conclusion, RA patients exhibited lower global leukocyte DNA methylation levels compared with CS. In both study groups, lower DNA methylation levels were associated with low methionine intake and an unfavorable cardiometabolic profile.

## Linked entities

- **Chemicals:** methionine (PubChem CID 876)
- **Diseases:** rheumatoid arthritis (MONDO:0008383)

## Full-text entities

- **Diseases:** RA (MESH:D001172), inflammatory (MESH:D007249), adiposity (MESH:D018205)
- **Chemicals:** Methyl-Donor (-), methionine (MESH:D008715), lipid (MESH:D008055)
- **Species:** Homo sapiens (human, species) [taxon 9606]

## Full text

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## Figures

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## References

49 references — full list in the complete paper: https://tomesphere.com/paper/PMC12898410/full.md

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Source: https://tomesphere.com/paper/PMC12898410