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Balkan J Med Genet. 2016 Jul 9;18(2):15-24. eCollection 2015 Dec 1.

Epigenetic alterations in patients with type 2 diabetes mellitus.

Author information

1
Department of Medical Genetics, Medical Faculty, Medical University of Sofia, Sofia, Bulgaria.
2
University Specialized Hospital for Active Treatment of Endocrinology 'Acad. Ivan Penchev,' Sofia, Bulgaria.
3
Institute of Molecular Biology, Bulgarian Academy of Sciences, Sofia, Bulgaria.
4
Department of Surgery, Medical Faculty, Medical University of Sofia, Sofia, Bulgaria.
5
Department of Pathophysiology, Medical Faculty, Medical University of Sofia, Sofia, Bulgaria.
6
Department of Pharmacology and Toxicology, Medical Faculty, Medical University of Sofia, Sofia, Bulgaria.
7
Clinical Laboratory, University Hospital 'Aleksandrovska,'Sofia, Bulgaria.

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.

KEYWORDS:

DNA methylation; Epigenetic changes; Methyl-CpG-binding domain protein 2 (MBD2); Stress and toxicity genes; Tumorigenesis; Type 2 diabetes mellitus (T2DM)

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