Genome-wide DNA methylation profiling of human diabetic peripheral neuropathy in
subjects with type 2 diabetes mellitus.
Authors Guo K, Elzinga S, Eid S, Figueroa-Romero C, Hinder LM, Pacut C, Feldman EL, Hur
Submitted By Junguk Hur on 10/14/2019
Status Published
Journal Epigenetics
Year 2019
Date Published 8/1/2019
Volume : Pages 14 : 766 - 779
PubMed Reference 31132961
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.