Genetic and Epigenetic Analysis of the MicroRNA-200 Family for Association with End Stage Renal Disease

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DNA methylation and miRNA profiles are associated with complex disease and are altered in uremic patients. We evaluated CpG sites, gene expression and SNPs of the microRNA-200 family and their target genes, including exploration of relevant methylation quantitative trait loci (meQTLs).

Quantitative DNA methylation was extracted from existing epigenome-wide association data (Illumina’s 450K Methylation array) for individuals with and without kidney disease (n=407). Following stringent quality control, a total of 14 significant CpG sites were identified within the MIR200 family, the most significant of which was cg23651812, (MIR429, P=4.1x10-45).

The top 20 predicted target genes were determined using miRDB for each miRNA (MIR141, MIR200A, MIR200B, MIR200C and MIR429). Target genes had 308 CpG sites with methylation data; the most significant two for MIR429 were cg11686204 in ELL2 and cg19038462 within ZEB1 (P=4.2x10-48).

RNA-Seq analysis was performed on renal transplant recipients and healthy controls using the Ion Proton™. RNA was selectively depleted for ribosomal RNA and up to 40 million reads were gained per sample. Differential methylation status was associated with expression of miRNA and their corresponding gene targets.

Genome-wide SNP data (n=561,233 SNPs; 372 individuals) from the Illumina 660K array was analysed in PLINK with QTL methylation data from the individual miRNA (n=14) and their target genes (n=308) CpG sites. No genome-wide significant cis-meQTLs were identified for miRNAs, but two were evident for ZEB2 (rs10200550, rs4347890), a target gene for MIR429. Genome-wide significant results (n=476 SNPs) were gained for 67 target genes (maximum P=9.98x10-32) which appear linked to these miRNA through having regulatory effects. CD36, the top-ranked gene, has previously been linked to kidney disease where it is suggested that it has a prominent role in the development of fibrosis.

We have provided a genomic map of the microRNA-200 family using novel data in order to assist in determining its association with ESRD.
Original languageEnglish
Publication statusPublished - 08 Nov 2015
EventAmerican Society of Nephrology 2015 Conference - San Diego, United States
Duration: 03 Nov 201508 Nov 2015


ConferenceAmerican Society of Nephrology 2015 Conference
Country/TerritoryUnited States
CitySan Diego

Bibliographical note

JASN - Journal of the American Society of Nephrology November 2015 Vol 26 Abstract Supplement, REF SA-PO491, p736A


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