Adipose tissue DNA methylome changes in development of new-onset diabetes after kidney transplantation

Abstract

Aim: New-onset diabetes after kidney transplant (NODAT) adversely impacts kidney allograft and patient survival. Epigenetic alterations in adipose tissue like DNA methylation may play a contributory role. Methods: Adipose tissue DNA of the patients with NODAT and their age, sex and BMI matched controls (nine each) were sequenced by reduced representation bisulfite sequencing. Differentially methylated CpGs (DMCs) and differentially methylated regions (DMRs) were studied. Results: Adipose tissue from the patients had reduced DNA methylation in intergenic and intronic regions. DMCs were found to be more hypomethylated in repeat regions and hypermethylated in CGIs and promoter region. About 900 DMRs were found and their associated genes were significantly enriched in 32 pathways, the top ones of which were associated with insulin resistance and inflammation. Some DMR or DMC genes have known T2DM associations. Conclusion: Changes in DNA methylation in adipose tissue may be suggestive of future NODAT.