Introduction Diabetic kidney disease (DKD) is a common complication of diabetes, characterised by progressive development of proteinuria and gradual loss of renal function. DKD is the most common cause of end-stage renal disease (requiring renal replacement therapy with either dialysis or transplant). Increasing evidence suggests that epigenetic alterations, including DNA methylation, are involved in the development and progression of DKD. This investigation compared methylation profiles from individuals with type 1 diabetes (T1D) and DKD to individuals with T1D and no evidence of renal failure, to identify potential methylation-based biomarkers of DKD. Methods Using the Zymo EZ DNA methylation kit to bisulphite treat the DNA and the Infinium HD Methylation Assay, 8 sample MethylationEPIC BeadChips from Illumina, the methylation status of >850,000 CpG sites, gene bodies, promoters and CpG islands were determined for 106 individuals with T1D. Of these, 66 cases had DKD and 40 controls had no evidence of renal disease. Cases and controls for this analysis were matched carefully for gender, age (1 year) and duration of diabetes. DNA obtained from each individual was treated in a consistent manner, with standard quality control applied. Results Methylation data was analysed using GenomeStudio v11. One gene, ACACB, showed a marked increase in methylation ( 0.12) in case samples compared to controls. ACACB has previously been linked with DKD. A further two DKD associated genes, ELMO1 and FKBP5, both had a decrease in methylation ( -0.03 and -0.07 respectively) in cases compared with controls. High concordance between duplicate samples (n=7) was also observed. Discussion We previously reported results for methylation sites differentially regulated in individuals with T1D with and without renal disease using Illumina’s HumanMethylation450K BeadChip and HumanMethylation27K BeadChip arrays. From these earlier studies, top-ranked genes with differential methylation profiles included ELMO1 and FKBP5. In this new analysis, both ELMO1 and FKBP5, demonstrated altered methylation status and direction of methylation change consistent with earlier studies. This project confirms and expands these results through more extensive coverage and adds new information on previously unexplored regions of the methylome.
|Publication status||Published - 2017|
|Event||1st European Alliance for Personalised Medicine Congress: Personalising Your Health: A Global Imperative! - Belfast, United Kingdom|
Duration: 27 Nov 2017 → 30 Nov 2017
|Conference||1st European Alliance for Personalised Medicine Congress|
|Period||27/11/2017 → 30/11/2017|