Genome-Wide Profiling of DNA Methylation and Gene Expression Identifies Candidate Genes for Human Diabetic Neuropathy (RRBS)

We perfomed transcriptomic and methylomic analysis of sural nerve biopsies from type 2 diabetic patients with neuropathy. Sural nerve transcriptomic and methylomic profiles were integrated and subsequent biological meaning investigated using KEGG pathway analysis of overlapping differentially expressed genes (DEGs) and differentially methylated genes (DMGs). A gene interation network was also generated including DEGs and DMGs, and common biological pathways were identified. Overall design: RNA/DNA were extracted from human sural nerves of type 2 diabetic patients with neuropathy and sequenced. Samples were initially grouped based on changes in myelinated fiber density (dMFD) over 52 weeks, representing nerve regeneration and degeneration and divided into three groups (regenerators with high nerve regeneration, degenerator with high nerve degeneration, and intermediate for all others) as described in a previous publication by our group (PMID: 24101696). However, unbiased clustering of the expression data in this study identifed three distinct groups, which were significantly different in terms of HbA1c levels (Group1: 8.66 +/- 1.59; Group2: 7.77 +/- 1.43; Group3: 8.67 +/- 1.44). Reduced representation bisulfate sequencing (RRBS) were also performed on the same sural nerve biopsies, belonging to Group1 and Group2.