ArticleEndocrine2020
Epigenetic mechanism in search for the pathomechanism of diabetic neuropathy development in diabetes mellitus type 1 (T1DM).
Article in Endocrine, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.
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Who cites it
12 citing papers in PubMed, 19 citations in OpenAlex.
- Diabetic neuropathy and wound healing: An update on epigenetic crosstalk.World journal of diabetes · 2025Review
- DNA methylation and 28 year incidence of two neuropathy phenotypes in type 1 diabetes: the Pittsburgh Epidemiology of Diabetes Complications cohort study.Diabetologia · 2025Article
- Unraveling the epigenetic fabric of type 2 diabetes mellitus: pathogenic mechanisms and therapeutic implications.Frontiers in endocrinology · 2024Review
- Mortality risk factors in newly diagnosed diabetic cardiac autonomic neuropathy.Clinical autonomic research : official journal of the Clinical Autonomic Research Society · 2023Article
- Article
- Review
- Epigenome-wide analysis of long-term air pollution exposure and DNA methylation in monocytes: results from the Multi-Ethnic Study of Atherosclerosis.Epigenetics · 2022Article
- Balance Analysis of Peripheral Neuropathy in Type 2 Diabetes Mellitus Based on Logistic Regression Equation.Scanning · 2022Article
- Genome-wide differentially methylated genes associated with posttraumatic stress disorder and longitudinal change in methylation in rape survivors.Translational psychiatry · 2021Article
- Genetic and Epigenomic Modifiers of Diabetic Neuropathy.International journal of molecular sciences · 2021Review
- Genome-Wide Association Study of 2,093 Cases With Idiopathic Polyneuropathy and 445,256 Controls Identifies First Susceptibility Loci.Frontiers in neurology · 2021Article
- Understanding Competitive Endogenous RNA Network Mechanism in Type 1 Diabetes Mellitus Using Computational and Bioinformatics Approaches.Diabetes, metabolic syndrome and obesity : targets and therapy · 2021Article
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Authors and funding
8 authors at 2 institutions in 1 country.
Funding
Abstract
objectiveThe aim of this study was to check the hypothesis concerning the crucial role of DNA methylation (one of the epigenetic mechanisms) within selected genes related to the destruction and regeneration of neural cells and its input in the pathogenesis of diabetic neuropathy, using a model of the DNA in peripheral blood cells.
methodsA cross-sectional, case-control study was conducted, consisting of 24 adult Type 1 Diabetes Melitus (T1DM) patients with autonomic neuropathy (CAN), 25 T1DM patients without neuropathy and 25 matched, healthy adults acting as a control (Ctrl). The Ewing's tests, using the ProSciCard apparatus (Mewicon CATEEM-Tec GmbH), was employed to assess the severity of the patients' symptoms of autonomic neuropathy. For DNA methylation analysis, DNA material of each sample DNA after bisulfite conversion was used for the hybridization of BeadChips (Infinium Methylation EPIC Kit, Illumina), and imaged on the Illumina HiScan. The changes in the expression of selected genes were examined using real-time PCR. Probes were labeled using fluorescein amidite, FAM (Thermo Fisher Scientific). Amplification was performed using the continuous fluorescence detection 7900 HT Fast Real-Time PCR system (Thermo Fisher Scientific). The expression ratio of the target mRNA was normalized to the level of 18s RNA and compared with the control. Statistical analysis was performed using Statistica version 13.1. The statistically significant results were recognized, with a value of p < 0.05.
resultsClinical analysis of the investigated groups revealed a significantly higher percentage of personal insulin pump users in the group without neuropathy. The glucose metabolic control, based on the HbA1c level analysis, was also significantly better in T1DM patients without CAN. The Bumphunter method for DNA methylation analysis showed statistically significant regions related to the genes involved in nerve regeneration ninjurin 2 (NINJ2) and functionality (BR serine/threonine kinase 2 BRSK2, claudin 4 CLDN4). When compared with T1DM patients without neuropathy, T1DM patients with neuropathy showed significantly increased methylation in the first NINJ2 axon, and a lower level of DNA methylation in the region of the first intron of BRSK2, as well as the CLDN4 5'UTR regions. The qRT-PCR results confirmed the decreased expression of NINJ2 and CLDN4 genes in patients with T1DM with CAN.
conclusionsThe different DNA methylation profiles, correlating with the expression of genes related to nervous tissue development and regeneration in patients with T1DM with autonomic neuropathy provide evidence for the role of epigenetic mechanisms promoting the development of CAN, a chronic complication of T1DM.
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