<abstract xmlns="http://www.w3.org/1999/xhtml"><p>Epigenetic changes, in particular DNA methylation processes, play a role in the pathogenesis and progression of type 2 diabetes mellitus (T2DM) linking genetic and environmental factors. To clarify this role, we have analyzed in patients with different duration of T2DM: (i) expression levels of methyl-CpG-binding domain protein 2 (<italic>MBD2</italic>) as marker of DNA methylation, and ii) methylation changes in 22 genes connected to cellular stress and toxicity. We have analyzed <italic>MBD2</italic> mRNA expression levels in16 patients and 12 controls and the methylation status of stress and toxicity genes in four DNA pools: (i) controls; (ii) newly-diagnosed T2DM patients; (iii) patients with T2DM duration of &lt;5 years and (iv) of >5 years. The <italic>MBD2</italic> expression levels were 10.4-times increased on average in T2DM patients compared to controls. Consistent increase in DNA methylation fraction with the increase in T2DM duration was observed in <italic>Prdx2</italic> and <italic>SCARA3</italic> genes, connected to oxidative stress protection and in <italic>BRCA1</italic> and <italic>Tp53</italic> tumor-suppressor genes. In conclusion, increased <italic>MBD2</italic> expression in patients indicated general dysregulation of DNA methylation in T2DM. The elevated methylation of <italic>Prdx2</italic> and <italic>SCARA3</italic> genes suggests disturbance in oxidative stress protection in T2DM. The increased methylation of <italic>BRCA1</italic> and <italic>Tp53</italic> genes unraveled an epigenetic cause for T2DM related increase in cancer risk.</p></abstract>

Epigenetic changes, in particular DNA methylation processes, play a role in the pathogenesis and progression of type 2 diabetes mellitus (T2DM) linking genetic and environmental factors. To clarify this role, we have analyzed in patients with different duration of T2DM: (i) expression levels of methyl-CpG-binding domain protein 2 (MBD2) as marker of DNA methylation, and ii) methylation changes in 22 genes connected to cellular stress and toxicity. We have analyzed MBD2 mRNA expression levels in16 patients and 12 controls and the methylation status of stress and toxicity genes in four DNA pools: (i) controls; (ii) newly-diagnosed T2DM patients; (iii) patients with T2DM duration of <5 years and (iv) of >5 years. The MBD2 expression levels were 10.4-times increased on average in T2DM patients compared to controls. Consistent increase in DNA methylation fraction with the increase in T2DM duration was observed in Prdx2 and SCARA3 genes, connected to oxidative stress protection and in BRCA1 and Tp53 tumor-suppressor genes. In conclusion, increased MBD2 expression in patients indicated general dysregulation of DNA methylation in T2DM. The elevated methylation of Prdx2 and SCARA3 genes suggests disturbance in oxidative stress protection in T2DM. The increased methylation of BRCA1 and Tp53 genes unraveled an epigenetic cause for T2DM related increase in cancer risk.

Epigenetic alterations in patients with type 2 diabetes mellitus

Department of Medical Genetics, Medical Faculty, Medical University of Sofia, Sofia,

University Specialized Hospital for Active Treatment of Endocrinology ‘Acad. Ivan Penchev,’ Sofia,

Institute of Molecular Biology, Bulgarian Academy of Sciences, Sofia,

Department of Surgery, Medical Faculty, Medical University of Sofia, Sofia,

Department of Pathophysiology, Medical Faculty, Medical University of Sofia, Sofia,

Department of Pharmacology and Toxicology, Medical Faculty, Medical University of Sofia, Sofia,

Clinical Laboratory, University Hospital ‘Aleksandrovska,’Sofia,

Balkan Journal of Medical Genetics

This article is distributed under the terms of the Creative Commons Attribution Non-Commercial License, which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

{"article-title":"Epigenetic alterations in patients with type 2 diabetes mellitus"}

Epigenetic changes, in particular DNA methylation processes, play a role in the pathogenesis and progression of type 2 diabetes mellitus (T2DM) linking genetic and environmental factors. To clarify this role, we have analyzed in patients with different duration of T2DM: (i) expression levels of methyl-CpG-binding domain protein 2 (MBD2) as marker of DNA methylation, and ii) methylation changes in 22 genes connected to cellular stress and toxicity. We have analyzed MBD2 mRNA expression levels in16 patients and 12 controls and the methylation status of stress and toxicity genes in four DNA pools: (i) controls; (ii) newly-diagnosed T2DM patients; (iii) patients with T2DM duration of 5 years. The MBD2 expression levels were 10.4-times increased on average in T2DM patients compared to controls. Consistent increase in DNA methylation fraction with the increase in T2DM duration was observed in Prdx2 and SCARA3 genes, connected to oxidative stress protection and in BRCA1 and Tp53 tumor-suppressor genes. In conclusion, increased MBD2 expression in patients indicated general dysregulation of DNA methylation in T2DM. The elevated methylation of Prdx2 and SCARA3 genes suggests disturbance in oxidative stress protection in T2DM. The increased methylation of BRCA1 and Tp53 genes unraveled an epigenetic cause for T2DM related increase in cancer risk.

Epigenetic changes, in particular DNA methylation processes, play a role in the pathogenesis and progression of type 2 diabetes mellitus (T2DM) linking genetic...

Epigenetic alterations in patients with type 2 diabetes mellitus

Article Category: Original Article

Published Online: Jul 09, 2016

Page range: 15 - 24

DOI: https://doi.org/10.1515/bjmg-2015-0081

Keywords
DNA methylation, Epigenetic changes, Methyl-CpG-binding domain protein 2 (), Stress and toxicity genes, Tumorigenesis, Type 2 diabetes mellitus (T2DM)

© 2016 Walter de Gruyter GmbH, Berlin/Boston

This article is distributed under the terms of the Creative Commons Attribution Non-Commercial License, which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

Epigenetic alterations in patients with type 2 diabetes mellitus

Article Category: Original Article

Published Online: Jul 09, 2016

Page range: 15 - 24

DOI: https://doi.org/10.1515/bjmg-2015-0081

KeywordsDNA methylation, Epigenetic changes, Methyl-CpG-binding domain protein 2 (), Stress and toxicity genes, Tumorigenesis, Type 2 diabetes mellitus (T2DM)

© 2016 Walter de Gruyter GmbH, Berlin/Boston

This article is distributed under the terms of the Creative Commons Attribution Non-Commercial License, which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

Keywords
DNA methylation, Epigenetic changes, Methyl-CpG-binding domain protein 2 (), Stress and toxicity genes, Tumorigenesis, Type 2 diabetes mellitus (T2DM)