Genome-wide DNA methylation profiling of human diabetic peripheral neuropathy in subjects with type 2 diabetes mellitus

Kai Guo, Sarah Elzinga, Stephanie Eid, Claudia Figueroa-Romero, Lucy M. Hinder, Crystal Pacut, Eva L. Feldman, Junguk Hur

Research output: Contribution to journalArticle

Abstract

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.

Original languageEnglish (US)
Pages (from-to)766-779
Number of pages14
JournalEpigenetics
Volume14
Issue number8
DOIs
StatePublished - Aug 3 2019

Fingerprint

DNA Fingerprinting
Diabetic Neuropathies
Peripheral Nervous System Diseases
DNA Methylation
Type 2 Diabetes Mellitus
Genome
Diabetes Complications
Nerve Fibers
Epigenomics
Sural Nerve
Biopsy
Glycerophospholipids
Biological Phenomena
Myelinated Nerve Fibers
Nerve Degeneration
Nerve Regeneration
Gene Expression Regulation
Mitogen-Activated Protein Kinases
Nervous System
Phenotype

Keywords

  • DNA methylation
  • RRBS
  • Type 2 diabetes
  • diabetic peripheral neuropathy
  • reduced representation bisulfite sequencing

ASJC Scopus subject areas

  • Molecular Biology
  • Cancer Research

Cite this

Genome-wide DNA methylation profiling of human diabetic peripheral neuropathy in subjects with type 2 diabetes mellitus. / Guo, Kai; Elzinga, Sarah; Eid, Stephanie; Figueroa-Romero, Claudia; Hinder, Lucy M.; Pacut, Crystal; Feldman, Eva L.; Hur, Junguk.

In: Epigenetics, Vol. 14, No. 8, 03.08.2019, p. 766-779.

Research output: Contribution to journalArticle

Guo, K, Elzinga, S, Eid, S, Figueroa-Romero, C, Hinder, LM, Pacut, C, Feldman, EL & Hur, J 2019, 'Genome-wide DNA methylation profiling of human diabetic peripheral neuropathy in subjects with type 2 diabetes mellitus', Epigenetics, vol. 14, no. 8, pp. 766-779. https://doi.org/10.1080/15592294.2019.1615352
Guo, Kai ; Elzinga, Sarah ; Eid, Stephanie ; Figueroa-Romero, Claudia ; Hinder, Lucy M. ; Pacut, Crystal ; Feldman, Eva L. ; Hur, Junguk. / Genome-wide DNA methylation profiling of human diabetic peripheral neuropathy in subjects with type 2 diabetes mellitus. In: Epigenetics. 2019 ; Vol. 14, No. 8. pp. 766-779.
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