title: Epigenetic alterations in patients with type 2 diabetes mellitus.
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 analyzedMBD2mRNA 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. TheMBD2expression 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 inPrdx2andSCARA3genes, connected to oxidative stress protection and inBRCA1andTp53tumor-suppressor genes. In conclusion, increasedMBD2expression in patients indicated general dysregulation of DNA methylation in T2DM. The elevated methylation ofPrdx2andSCARA3genes suggests disturbance in oxidative stress protection in T2DM. The increased methylation ofBRCA1andTp53genes unraveled an epigenetic cause for T2DM related increase in cancer risk.
authors: Department of Medical Genetics, Medical Faculty, Medical University of Sofia, Sofia, Bulgaria.
authors: S
authors: S
authors: Karachanak-Yankova
authors: University Specialized Hospital for Active Treatment of Endocrinology 'Acad. Ivan Penchev,' Sofia, Bulgaria.
authors: R
authors: R
authors: Dimova
authors: Department of Medical Genetics, Medical Faculty, Medical University of Sofia, Sofia, Bulgaria.
authors: D
authors: D
authors: Nikolova
authors: Department of Medical Genetics, Medical Faculty, Medical University of Sofia, Sofia, Bulgaria.
authors: D
authors: D
authors: Nesheva
authors: Institute of Molecular Biology, Bulgarian Academy of Sciences, Sofia, Bulgaria.
authors: M
authors: M
authors: Koprinarova
authors: Department of Surgery, Medical Faculty, Medical University of Sofia, Sofia, Bulgaria.
authors: S
authors: S
authors: Maslyankov
authors: Department of Pathophysiology, Medical Faculty, Medical University of Sofia, Sofia, Bulgaria.
authors: R
authors: R
authors: Tafradjiska
authors: Department of Pharmacology and Toxicology, Medical Faculty, Medical University of Sofia, Sofia, Bulgaria.
authors: P
authors: P
authors: Gateva
authors: Clinical Laboratory, University Hospital 'Aleksandrovska,'Sofia, Bulgaria.
authors: M
authors: M
authors: Velizarova
authors: Department of Medical Genetics, Medical Faculty, Medical University of Sofia, Sofia, Bulgaria.
authors: Z
authors: Z
authors: Hammoudeh
authors: University Specialized Hospital for Active Treatment of Endocrinology 'Acad. Ivan Penchev,' Sofia, Bulgaria.
authors: N
authors: N
authors: Stoynev
authors: Department of Medical Genetics, Medical Faculty, Medical University of Sofia, Sofia, Bulgaria.
authors: D
authors: D
authors: Toncheva
authors: University Specialized Hospital for Active Treatment of Endocrinology 'Acad. Ivan Penchev,' Sofia, Bulgaria.
authors: T
authors: T
authors: Tankova
authors: Department of Medical Genetics, Medical Faculty, Medical University of Sofia, Sofia, Bulgaria.
authors: I
authors: I
authors: Dimova
keywords: DNA methylation; Epigenetic changes; Methyl-CpG-binding domain protein 2 (MBD2); Stress and toxicity genes; Tumorigenesis; Type 2 diabetes mellitus (T2DM)