Genome-Wide DNA Methylation and LncRNA-Associated DNA Methylation in Metformin-Treated and -Untreated Diabetes

Metformin, which is used as a first line treatment for type 2 diabetes mellitus (T2DM), has been shown to affect epigenetic patterns. In this study, we investigated the DNA methylation and potential lncRNA modifications in metformin-treated and newly diagnosed adults with T2DM. Genome-wide DNA methy...

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Main Authors: Wendy L. Solomon, Stanton B. E. Hector, Shanel Raghubeer, Rajiv T. Erasmus, Andre P. Kengne, Tandi E. Matsha
Format: Article
Language:English
Published: MDPI AG 2020-09-01
Series:Epigenomes
Subjects:
Online Access:https://www.mdpi.com/2075-4655/4/3/19
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author Wendy L. Solomon
Stanton B. E. Hector
Shanel Raghubeer
Rajiv T. Erasmus
Andre P. Kengne
Tandi E. Matsha
author_facet Wendy L. Solomon
Stanton B. E. Hector
Shanel Raghubeer
Rajiv T. Erasmus
Andre P. Kengne
Tandi E. Matsha
author_sort Wendy L. Solomon
collection DOAJ
description Metformin, which is used as a first line treatment for type 2 diabetes mellitus (T2DM), has been shown to affect epigenetic patterns. In this study, we investigated the DNA methylation and potential lncRNA modifications in metformin-treated and newly diagnosed adults with T2DM. Genome-wide DNA methylation and lncRNA analysis were performed from the peripheral blood of 12 screen-detected and 12 metformin-treated T2DM individuals followed by gene ontology (GO) and KEGG pathway analysis. Differentially methylated regions (DMRs) observed showed 22 hypermethylated and 11 hypomethylated DMRs between individuals on metformin compared to screen-detected subjects. Amongst the hypomethylated DMR regions were the SLC gene family, specifically, SLC25A35 and SLC28A1. Fifty-seven lncRNA-associated DNA methylation regions included the mitochondrial ATP synthase-coupling factor 6 (ATP5J). Functional gene mapping and pathway analysis identified regions in the axon initial segment (AIS), node of Ranvier, cell periphery, cleavage furrow, cell surface furrow, and stress fiber. In conclusion, our study has identified a number of DMRs and lncRNA-associated DNA methylation regions in metformin-treated T2DM that are potential targets for therapeutic monitoring in patients with diabetes.
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spelling doaj.art-a8d7db81f8104bd786d016335df68dc62023-11-20T12:12:32ZengMDPI AGEpigenomes2075-46552020-09-01431910.3390/epigenomes4030019Genome-Wide DNA Methylation and LncRNA-Associated DNA Methylation in Metformin-Treated and -Untreated DiabetesWendy L. Solomon0Stanton B. E. Hector1Shanel Raghubeer2Rajiv T. Erasmus3Andre P. Kengne4Tandi E. Matsha5SAMRC/CPUT/Cardiometabolic Health Research Unit, Department of Biomedical Sciences, Faculty of Health and Wellness Science, Cape Peninsula University of Technology, P.O. Box 1906, Bellville, Cape Town 7530, South AfricaSAMRC/CPUT/Cardiometabolic Health Research Unit, Department of Biomedical Sciences, Faculty of Health and Wellness Science, Cape Peninsula University of Technology, P.O. Box 1906, Bellville, Cape Town 7530, South AfricaSAMRC/CPUT/Cardiometabolic Health Research Unit, Department of Biomedical Sciences, Faculty of Health and Wellness Science, Cape Peninsula University of Technology, P.O. Box 1906, Bellville, Cape Town 7530, South AfricaDivision of Chemical Pathology, Faculty of Health Sciences, National Health Laboratory Service (NHLS) and University of Stellenbosch, Cape Town 7505, South AfricaNon-Communicable Diseases Research Unit, South African Medical Research Council, Cape Town 7505, South AfricaSAMRC/CPUT/Cardiometabolic Health Research Unit, Department of Biomedical Sciences, Faculty of Health and Wellness Science, Cape Peninsula University of Technology, P.O. Box 1906, Bellville, Cape Town 7530, South AfricaMetformin, which is used as a first line treatment for type 2 diabetes mellitus (T2DM), has been shown to affect epigenetic patterns. In this study, we investigated the DNA methylation and potential lncRNA modifications in metformin-treated and newly diagnosed adults with T2DM. Genome-wide DNA methylation and lncRNA analysis were performed from the peripheral blood of 12 screen-detected and 12 metformin-treated T2DM individuals followed by gene ontology (GO) and KEGG pathway analysis. Differentially methylated regions (DMRs) observed showed 22 hypermethylated and 11 hypomethylated DMRs between individuals on metformin compared to screen-detected subjects. Amongst the hypomethylated DMR regions were the SLC gene family, specifically, SLC25A35 and SLC28A1. Fifty-seven lncRNA-associated DNA methylation regions included the mitochondrial ATP synthase-coupling factor 6 (ATP5J). Functional gene mapping and pathway analysis identified regions in the axon initial segment (AIS), node of Ranvier, cell periphery, cleavage furrow, cell surface furrow, and stress fiber. In conclusion, our study has identified a number of DMRs and lncRNA-associated DNA methylation regions in metformin-treated T2DM that are potential targets for therapeutic monitoring in patients with diabetes.https://www.mdpi.com/2075-4655/4/3/19metforminDNA methylationlncRNAdiabetes mellitusAfrica
spellingShingle Wendy L. Solomon
Stanton B. E. Hector
Shanel Raghubeer
Rajiv T. Erasmus
Andre P. Kengne
Tandi E. Matsha
Genome-Wide DNA Methylation and LncRNA-Associated DNA Methylation in Metformin-Treated and -Untreated Diabetes
Epigenomes
metformin
DNA methylation
lncRNA
diabetes mellitus
Africa
title Genome-Wide DNA Methylation and LncRNA-Associated DNA Methylation in Metformin-Treated and -Untreated Diabetes
title_full Genome-Wide DNA Methylation and LncRNA-Associated DNA Methylation in Metformin-Treated and -Untreated Diabetes
title_fullStr Genome-Wide DNA Methylation and LncRNA-Associated DNA Methylation in Metformin-Treated and -Untreated Diabetes
title_full_unstemmed Genome-Wide DNA Methylation and LncRNA-Associated DNA Methylation in Metformin-Treated and -Untreated Diabetes
title_short Genome-Wide DNA Methylation and LncRNA-Associated DNA Methylation in Metformin-Treated and -Untreated Diabetes
title_sort genome wide dna methylation and lncrna associated dna methylation in metformin treated and untreated diabetes
topic metformin
DNA methylation
lncRNA
diabetes mellitus
Africa
url https://www.mdpi.com/2075-4655/4/3/19
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