Abstract
DNA methylation and miRNAs are associated with complex disease and are altered in uremic patients. This study investigated association between DNA methylation and chronic kidney disease (CKD) using a relatively large-scale, case-control approach.
The Infinium® HumanMethylation 450K BeadChip array (Illumina, Inc, USA) was used to analyse DNA methylation across the methylome in 255 CKD cases and 152 unaffected controls (MDRD eGFR>60 mL/min/1.73m2). Following stringent quality control, methylation levels were analysed and results adjusted for multiple testing using the Benjamini Hochberg approach. Quantitative methylation values were obtained at single-CpG level for 2,249 sites associated with miRNA genes across the genome.
Six miRNA genes on autosomes were selected for fine mapping and replication based on P<10^-5 in the discovery collection; MIR550-2, MIR940, MIR34A, MIR429, MIR141, and MIR329-2. Bidirectional Sanger sequencing of the genetic region immediately flanking CpG sites of interest in 23 cases and 23 controls for five of these miRNA genes revealed 37 methylated CpG sites; MIR550-2 did not generate robust sequencing results. Sequencing of untreated genomic DNA revealed 13 known and two novel SNPs flanking the CpG site of interest. Replication using an independent cohort of cases with CKD compared to a general control population (n=400) on the sample 450K platform revealed additional support for methylation at these miRNA loci influencing CKD.
Epigenetic features such as DNA methylation and miRNAs may cause or accelerate renal injury. This pilot study has identified several miRNA genes with differential methylation profiles that are associated with CKD. Comparison to RNA-seq data in a subset of these individuals will help elicit the functional effect of the novel findings reported in this abstract on the pathogenesis or progression of CKD.
Original language | English |
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Publication status | Published - 2013 |
Event | American Society of Nephrology - Atlanta, United States Duration: 07 Nov 2013 → 10 Nov 2013 |
Conference
Conference | American Society of Nephrology |
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Country/Territory | United States |
City | Atlanta |
Period | 07/11/2013 → 10/11/2013 |