MicroRNAs are understood to play a functional role within the establishment of epigenetic marks and are in turn under epigenetic control. Emerging evidence suggests microRNAs are vital for both kidney development and renal function. This study aimed to identify differential methylation affecting microRNAs in patients with end-stage renal disease (ESRD). Methylation status was determined for 485,577 unique CpG sites in 105 individuals with ESRD and 52 donor controls with no evidence of renal disease using the HumanMethylation450K BeadChip array (Illumina). Statistically significant associations (P<10-8) were observed between case and control groups for both unique CpG sites within microRNAs and their target genes, identified using miRDB (an online database for microRNA target prediction and functional annotations). CpG sites (n=111) within top-ranked microRNAs (n=42) alongside 848 CpGs in 198 target genes were evaluated in genotyped renal transplant samples to detect methylation quantitative trait loci (meQTLs) associated with ESRD. Following allelic association PLINK analysis, 116 SNPs were determined from the investigated CpG sites, 12 of which were located in genes previously linked with renal disease or microRNAs. Blood-derived Ion Total RNA-Seq v2 analysis was performed on 10 ESRD samples and 29 controls (with no evidence of renal disease) to determine the expression levels of the microRNAs and target genes. Sequencing was completed using the Ion Proton™ (Thermo Fisher Scientific) and the most significant results were MIR548H4 (5.79x10-6) and WASF3 (5.59x10-9) respectively, showing increased expression within the ESRD samples. This study has identified microRNA-related differential methylation with supporting gene expression data, associated with ESRD.
|Publication status||Published - Sep 2016|
|Event||Irish Society of Human Genetics 2016 - |
Duration: 09 Sep 2016 → 09 Sep 2016
|Conference||Irish Society of Human Genetics 2016|
|Period||09/09/2016 → 09/09/2016|