Effects of metformin on TCF7L2 gene DNA methylation alterations in individuals with Type 2 diabetes mellitus: Effects of metformin on TCF7L2 gene DNA methylation alterations

Harem Othman Smail; Sakar Ahmed Abdullah

doi:10.63841/iue3261033

Authors

Harem Othman Smail Department of Biology, Faculty of Science and Health, Koya University, Koya 44023, Kurdistan Region – F.R. IRAQ Author https://orcid.org/0000-0001-9867-4289
Sakar Ahmed Abdullah Medical Laboratory Department, College of health and medical technology, Sulaimani Polytechnic University, Sulaimani, IRAQ Author https://orcid.org/0000-0002-5223-201X

DOI:

https://doi.org/10.63841/iue3261033

Keywords:

TCF7L2 gene, metformin, T2DM, DNA methylation, Methylation-specific PCR.

Abstract

DNA methylation is an epigenetic factor that controls gene expression and contributes to diseases such as type 2 diabetes mellitus. The diabetic treatment metformin contributes to the DNA methylation level of the transcription Factor T-cell factor-7 like-2 (TCF7L2) in diabetic patients. TCF7L2 is a transcription factor that regulates the expression of genes involved in lipid and glucose metabolism, such as insulin production in pancreatic β-cells and Glucagon in α-cells through Wnt/β-catenin.

We aimed to determine the effect of Metformin on the DNA methylation level of gene TCF7L2 in T2DM. For this purpose, fifty blood samples (25 type 2 diabetes mellitus taking Metformin and 25 without taking Metformin) were collected from both genders from Koya City, Kurdistan region of Iraq, from August 2021 to December 2021 in a private laboratory from diabetic patients confirmed by HbA1c blood test.

DNA methylation levels were determined by using methylation-specific PCR(MSP); for this purpose, a couple of the primers for amplification of both methylated and unmethylated regions were used for the promoter region for detecting the methylation level of CpG sites at (-99, -119, -123, -246, 266). For statistical analysis, the Mann–Whitney U test and Spearman’s correlations were utilized.

The results showed no significant difference in DNA methylation levels between metformin users (48% methylated) and non-users (52% methylated) (p = 0.155). Additionally, ROC analysis (AUC = 0.6, p = 0.1) was statistically insignificant.

Based on the TCF7L2 gene of the T2DM patients, we can conclude that there was no correlation between the use of metformin and DNA methylation level.

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Author Biographies

Harem Othman Smail , Department of Biology, Faculty of Science and Health, Koya University, Koya 44023, Kurdistan Region – F.R. IRAQ

Harem Othman Smail is an Assistant Professor in the Department of Biology, Faculty of Science and Health, University of Koya. He received a B.Sc. degree in Biology, an M.Sc. degree in Molecular Biology, and a Ph.D. degree in Molecular Biology. His research interests are in genetics, molecular biology, and epigenetics.
Sakar Ahmed Abdullah, Medical Laboratory Department, College of health and medical technology, Sulaimani Polytechnic University, Sulaimani, IRAQ

Sakar Ahmed Abdullah is a lecturer in the Medical Laboratory Department, College of Health and Medical Technology, Sulaimani Polytechnic University. She received a B.Sc. degree in Biology, an M.Sc. degree in Immunology, and a Ph.D. degree in Molecular Biology. Her research interests are in Immunology, Molecular Biology, and Epigenetics.

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Effects of metformin on TCF7L2 gene DNA methylation alterations in individuals with Type 2 diabetes mellitus