Genome-wide profiling of DNA methylation and gene expression identifies candidate genes for human diabetic neuropathy

Kai Guo, Stephanie A. Eid, Sarah E. Elzinga, Crystal Pacut, Eva L. Feldman, Junguk Hur

Research output: Contribution to journalArticle

1 Scopus citations

Abstract

BACKGROUND: 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. RESULTS: 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. CONCLUSION: 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.

Original languageEnglish (US)
Pages (from-to)123
Number of pages1
JournalClinical Epigenetics
Volume12
Issue number1
DOIs
StatePublished - Aug 12 2020

Keywords

  • DNA methylation
  • Diabetic peripheral neuropathy
  • Epigenetics
  • Gene expression
  • HbA1c
  • Human
  • Transcriptomics
  • Type 2 diabetes

ASJC Scopus subject areas

  • Molecular Biology
  • Genetics
  • Developmental Biology
  • Genetics(clinical)

Fingerprint Dive into the research topics of 'Genome-wide profiling of DNA methylation and gene expression identifies candidate genes for human diabetic neuropathy'. Together they form a unique fingerprint.

  • Cite this