PhD Scientific Days 2026

Molecular Medicine 4.

Hyperglycemia- and Depression-Associated DNA Methylation Changes in Type 2 Diabetes Patients

Name of the presenter

Fóthi, Ábel

Institute/workplace of the presenter

Department of Molecular Biology, Institute of Biochemistry and Molecular Biology, Semmelweis University

Authors

Ábel Fóthi¹, Giuseppe Fanelli², Anikó Somogyi³, Géza Nagy³, Zsolt Rónai¹, Mária Sasvári-Székely¹, Janita Bralten², Barbara Franke², Csaba Barta¹
1: Department of Molecular Biology, Institute of Biochemistry and Molecular Biology, Semmelweis University
2: Department of Human Genetics, Radboud University Medical Center, Nijmegen, The Netherlands
3: Department of Internal Medicine and Haematology, Semmelweis University

Text of the abstract

Introduction
Type 2 diabetes is associated not only with metabolic dysfunction but also with an increased prevalence of psychiatric disorders, particularly depression. Epigenetic mechanisms, especially DNA methylation, may play a key role in linking these conditions.
Aims
This study aimed to identify DNA methylation changes associated with hyperglycemia and depression in individuals with type 2 diabetes.
Methods
Data collection was performed within the framework of the PRIME (Prevention and Remediation of Insulin Multimorbidity in Europe) project and included 208 Hungarian patients with type 2 diabetes (50% male; mean age: 60.9 years).
DNA was isolated from buccal mucosa samples, and genome-wide DNA methylation levels were assessed using the Illumina EPICv2 array. Data processing and quality control were performed in R using the SeSAMe pipeline.
Associations between methylation levels and clinical, metabolic, and psychological variables were evaluated using regression models adjusted for age, sex, smoking status, and leukocyte composition.
Results
The CpG site cg19693031 in the TXNIP gene showed the strongest association with hyperglycemia (p = 9.67 × 10⁻⁷). This gene is known to play a role in regulating pancreatic beta-cell function.
Among patients with clinical depression, the most significant differential methylation was observed at cg16524049 in the LMX1A gene (p = 9.51 × 10⁻⁹), which is involved in the development of dopaminergic neurons. The second most significant site was cg19068644 in the OSBPL5 gene (p = 1.27 × 10⁻⁷), a gene known to exhibit long-lasting DNA methylation changes following in utero starvation exposure.
These findings reveal novel, diabetes-specific associations between DNA methylation and depression.
Conclusion
Our results highlight distinct epigenetic alterations associated with hyperglycemia and depression in type 2 diabetes, offering new insights into the biological mechanisms underlying psychiatric comorbidities in these patients.
Funding
This work was supported by the University Research Scholarship Program (grant code: 2025-2.1.1-EKÖP-2025-00014) of the Ministry of Culture and Innovation, funded by the National Research, Development and Innovation Fund.
This project has received funding from the European Union’s Horizon 2020 research and innovation programme under grant agreement No 847879.