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Publication
Genome-wide profiling of DNA methylation and gene expression identifies
candidate genes for human diabetic neuropathy.
Authors Guo K, Eid SA, Elzinga SE, Pacut C, Feldman EL, Hur J
Submitted By Submitted Externally on 9/28/2020
Status Published
Journal Clinical epigenetics
Year 2020
Date Published 8/1/2020
Volume : Pages 12 : 123
PubMed Reference 32787975
Abstract Diabetic peripheral neuropathy (DPN) is the most common complication of type 2
diabetes (T2D). Although the cellular and molecular mechanisms of DPN are poorly
understood, we and others have shown that altered gene expression and DNA
methylation are implicated in disease pathogenesis. However, how DNA methylation
might functionally impact gene expression and contribute to nerve damage remains
unclear. Here, we analyzed genome-wide transcriptomic and methylomic profiles of
sural nerves from T2D patients with DPN., Unbiased clustering of transcriptomics
data separated samples into groups, which correlated with HbA1c levels.
Accordingly, we found 998 differentially expressed genes (DEGs) and 929
differentially methylated genes (DMGs) between the groups with the highest and
lowest HbA1c levels. Functional enrichment analysis revealed that DEGs and DMGs
were enriched for pathways known to play a role in DPN, including those related
to the immune system, extracellular matrix (ECM), and axon guidance. To
understand the interaction between the transcriptome and methylome in DPN, we
performed an integrated analysis of the overlapping genes between DEGs and DMGs.
Integrated functional and network analysis identified genes and pathways
modulating functions such as immune response, ECM regulation, and PI3K-Akt
signaling., These results suggest for the first time that DNA methylation is a
mechanism regulating gene expression in DPN. Overall, DPN patients with high
HbA1c have distinct alterations in sural nerve DNA methylome and transcriptome,
suggesting that optimal glycemic control in DPN patients is an important factor
in maintaining epigenetic homeostasis and nerve function.





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