Introduction: DNA methylation is an important epigenetic modification that does not change the DNA sequence. DNA methylation profiles have been associated with complex disease and are altered in uraemic patients. This study investigated association between DNA methylation and chronic kidney disease (CKD) using a case-control approach. Methods: The Infinium® methylation 450K BeadChip array (Illumina, Inc, USA) was used to analyse DNA methylation across the methylome in 255 CKD cases and 152 controls (MDRD eGFR>60 mL/min/1.73m2). Following stringent quality control, methylation levels were analysed and results adjusted for multiple testing. Results: Quantitative methylation values were obtained at single-CpG level for 485,577 features, encompassing all designable genes, including promoter, 5', and 3' regions, CpG islands outside coding regions, and miRNA promoter regions. Differential DNA methylation was observed in 23 genes where more than one CpG site per gene was identified with Padjusted<10-8. Top ranked genes are involved in cell migration, cell proliferation, vesicle trafficking and replication. Of particular interest are genes such as ELMO1, CUX1, PTPRN2, and PRKAG2, which have all been previously highlighted from experimental (functional and genetic) studies of renal disease. Discussion: Epigenetic modifications have emerged as both a cause and consequence of disease. They may be altered by drugs, environmental factors and disruption of homeostasis. Patients with CKD have a uraemic cellular milieu which may modify DNA methylation. However, DNA methylation may also cause or accelerate renal injury. This pilot study has identified 23 strongly significant genes associated with CKD. Further work is required to elicit the effect of altered methylation status at these loci on the pathogenesis or progression of CKD.
|Publication status||Published - 2013|
|Event||The Renal Association and British Transplant Society Renal Congress 2013 - , United Kingdom|
Duration: 01 Jan 2013 → …
|Conference||The Renal Association and British Transplant Society Renal Congress 2013|
|Period||01/01/2013 → …|