Ivanka DimovaMedical University Sofia, Bulgaria
Title: Increased methylation of tumor-suppressor genes in patients with type 2 diabetes mellitus
Background: Genome-Wide Association Studies (GWAS) has identified and confirmed a number of genetic variants for susceptibility to type 2 diabetes mellitus (T2DM). However, these findings explain only small part of the overall genetic risk for the disease, which necessitates new studies to clarify the relationship between genetic factors and the clinical manifestation. Epigenetic factors are most likely involved in the complex interaction between genes and the environment. Studies on epigenetic factors in the genesis of the complex diseases are not yet sufficient. Therefore, epigenetic studies could shed light on understanding their pathogenesis. The most studied mechanisms that are known to affect the epigenome are DNA methylation, histone modification, and aberrant expression of microRNAs. Objective: We aimed to determine DNA methylation levels of genes connected to cellular stress and tumorigenesis during the course of T2DM in order to understand the role of epigenetic regulation in their development. Materials and methods: We have performed analysis for promoter methylation of 22 such genes in blood samples of patients with these two diseases, compared with healthy controls using Human Stress & Toxicity Pathway Finder EpiTect Methyl II Signature PCR Array. The method is based on detection of remaining input DNA after cleavage with methylation-sensitive and methylation-dependent restriction enzyme. The relative fractions of methylated and unmethylated DNA are subsequently determined by comparing the amount in each digest with that of a mock (no enzymes added) digest using a ?Ct method and mathematical quotation. Results and conclusion: We revealed highly increased promoter methylation (associated with gene silencing) of BRCA1, MSH2 and CDKN1a genes in T2DM patients. This pilot study paves the way to better understand the complex pathogenesis of diseases with the contribution of epigenetic dysregulation.
Ivanka Dimova has completed her PhD at the age of 32 years from Medical University Sofia, Bulgaria. She is the head of Laboratory of Genomic diagnostics of Medical University Sofia since 2015. She has over 100 publications that have been cited over 800 times, and her publication h-index is 17. He has been serving as an editorial board member of several reputed journals.