Genome-wide DNA methylation profiling of human diabetic peripheral neuropathy in subjects with type 2 diabetes mellitus
DNA methylation is an epigenetic mechanism important for the regulation of gene expression, which plays a vital role in the interaction between genetic and environmental factors. Aberrant epigenetic changes are implicated in the pathogenesis of diabetes and diabetic complications, but the role of DN...
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| Format: | Article |
| Language: | English |
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Taylor & Francis Group
2019-08-01
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| Series: | Epigenetics |
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| Online Access: | http://dx.doi.org/10.1080/15592294.2019.1615352 |
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| author | Kai Guo Sarah Elzinga Stephanie Eid Claudia Figueroa-Romero Lucy M. Hinder Crystal Pacut Eva L. Feldman Junguk Hur |
| author_facet | Kai Guo Sarah Elzinga Stephanie Eid Claudia Figueroa-Romero Lucy M. Hinder Crystal Pacut Eva L. Feldman Junguk Hur |
| author_sort | Kai Guo |
| collection | DOAJ |
| description | DNA methylation is an epigenetic mechanism important for the regulation of gene expression, which plays a vital role in the interaction between genetic and environmental factors. Aberrant epigenetic changes are implicated in the pathogenesis of diabetes and diabetic complications, but the role of DNA methylation in diabetic peripheral neuropathy (DPN) is not well understood. Therefore, our aim in this study was to explore the role of DNA methylation in the progression of DPN in type 2 diabetes. We compared genome-wide DNA methylation profiles of human sural nerve biopsies from subjects with stable or improving nerve fibre counts to biopsies from subjects with progressive loss of nerve fibres. Nerve fibre counts were determined by comparing myelinated nerve fibre densities between an initial and repeat biopsy separated by 52 weeks. Subjects with significant nerve regeneration (regenerators) and subjects with significant nerve degeneration (degenerators) represent the two extreme DPN phenotypes. Using reduced representation bisulfite sequencing, we identified 3,460 differentially methylated CpG dinucleotides between the two groups. The genes associated with differentially methylated CpGs were highly enriched in biological processes that have previously been implicated in DPN such as nervous system development, neuron development, and axon guidance, as well as glycerophospholipid metabolism and mitogen-activated protein kinase (MAPK) signalling. These findings are the first to provide a comprehensive analysis of DNA methylation profiling in human sural nerves of subjects with DPN and suggest that epigenetic regulation has an important role in the progression of this prevalent diabetic complication. |
| first_indexed | 2024-03-11T23:07:02Z |
| format | Article |
| id | doaj.art-ff7f57880800477aba718930fa659f0e |
| institution | Directory Open Access Journal |
| issn | 1559-2294 1559-2308 |
| language | English |
| last_indexed | 2024-03-11T23:07:02Z |
| publishDate | 2019-08-01 |
| publisher | Taylor & Francis Group |
| record_format | Article |
| series | Epigenetics |
| spelling | doaj.art-ff7f57880800477aba718930fa659f0e2023-09-21T13:09:22ZengTaylor & Francis GroupEpigenetics1559-22941559-23082019-08-0114876677910.1080/15592294.2019.16153521615352Genome-wide DNA methylation profiling of human diabetic peripheral neuropathy in subjects with type 2 diabetes mellitusKai Guo0Sarah Elzinga1Stephanie Eid2Claudia Figueroa-Romero3Lucy M. Hinder4Crystal Pacut5Eva L. Feldman6Junguk Hur7University of North DakotaUniversity of MichiganUniversity of MichiganUniversity of MichiganUniversity of MichiganUniversity of MichiganUniversity of MichiganUniversity of North DakotaDNA methylation is an epigenetic mechanism important for the regulation of gene expression, which plays a vital role in the interaction between genetic and environmental factors. Aberrant epigenetic changes are implicated in the pathogenesis of diabetes and diabetic complications, but the role of DNA methylation in diabetic peripheral neuropathy (DPN) is not well understood. Therefore, our aim in this study was to explore the role of DNA methylation in the progression of DPN in type 2 diabetes. We compared genome-wide DNA methylation profiles of human sural nerve biopsies from subjects with stable or improving nerve fibre counts to biopsies from subjects with progressive loss of nerve fibres. Nerve fibre counts were determined by comparing myelinated nerve fibre densities between an initial and repeat biopsy separated by 52 weeks. Subjects with significant nerve regeneration (regenerators) and subjects with significant nerve degeneration (degenerators) represent the two extreme DPN phenotypes. Using reduced representation bisulfite sequencing, we identified 3,460 differentially methylated CpG dinucleotides between the two groups. The genes associated with differentially methylated CpGs were highly enriched in biological processes that have previously been implicated in DPN such as nervous system development, neuron development, and axon guidance, as well as glycerophospholipid metabolism and mitogen-activated protein kinase (MAPK) signalling. These findings are the first to provide a comprehensive analysis of DNA methylation profiling in human sural nerves of subjects with DPN and suggest that epigenetic regulation has an important role in the progression of this prevalent diabetic complication.http://dx.doi.org/10.1080/15592294.2019.1615352type 2 diabetesdiabetic peripheral neuropathydna methylationreduced representation bisulfite sequencingrrbs |
| spellingShingle | Kai Guo Sarah Elzinga Stephanie Eid Claudia Figueroa-Romero Lucy M. Hinder Crystal Pacut Eva L. Feldman Junguk Hur Genome-wide DNA methylation profiling of human diabetic peripheral neuropathy in subjects with type 2 diabetes mellitus Epigenetics type 2 diabetes diabetic peripheral neuropathy dna methylation reduced representation bisulfite sequencing rrbs |
| title | Genome-wide DNA methylation profiling of human diabetic peripheral neuropathy in subjects with type 2 diabetes mellitus |
| title_full | Genome-wide DNA methylation profiling of human diabetic peripheral neuropathy in subjects with type 2 diabetes mellitus |
| title_fullStr | Genome-wide DNA methylation profiling of human diabetic peripheral neuropathy in subjects with type 2 diabetes mellitus |
| title_full_unstemmed | Genome-wide DNA methylation profiling of human diabetic peripheral neuropathy in subjects with type 2 diabetes mellitus |
| title_short | Genome-wide DNA methylation profiling of human diabetic peripheral neuropathy in subjects with type 2 diabetes mellitus |
| title_sort | genome wide dna methylation profiling of human diabetic peripheral neuropathy in subjects with type 2 diabetes mellitus |
| topic | type 2 diabetes diabetic peripheral neuropathy dna methylation reduced representation bisulfite sequencing rrbs |
| url | http://dx.doi.org/10.1080/15592294.2019.1615352 |
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