Skip to main content

Table 6 Methylation studies in diabetic kidney disease

From: Genomic approaches in the search for molecular biomarkers in chronic kidney disease

PMID Author Year Sample Cases (n) Controls (n) Ethnicity Methodology Main findings
25850930 Swan 2015 Blood DKD (n = 100)
DKD + ESRD (n = 50) RRT
Diabetes and no renal disease (n = 100) White 27 K
450 K
Mitochondrial Genes
Identification of 450 CpGs differentially methylated
T1DM-DKD: 54 probes (51 genes) significant (p < 10−8)
PMPCB, AUH and TSFM: DMRs at more than one CpG
ESRD: identification of 755 CpG probes in 374 (p ≤ 10−8). Forty-three top-ranked CpG sites for DKD were also differentially methylated identified in the subgroup of patients with ESRD
24098934 Ko 2013 Tubule epithelial cells Discovery: CKD (both HT and DKD) (n = 14)
Replication: DKD (n = 21)
Discovery: Healthy (n = 14)
Replication: Non-DKD
Mixed Discovery: MSP-HELP
Replication: MassArray Epityper (INTERNAL) and 450 K (external)
Identification of 4751 DMRs identified in Discovery, 1535 unique genes, 70% showed hypomethylation in CKD
Confirmation of 1061 unique genes were identified in the replication cohort (98% of genes found in the discovery analysis)
COLIVA1, along with 5 other gene loci, had mRNA/protein analyses performed
DMRs enriched in kidney-specific gene regulatory regions (mainly enhancers/binding motifs for renal-specific transcription factors
21150313 Sapienza 2011 Saliva DM-ESRD (n = 23) DM (n = 23) African American
Hispanic American
27 K array 27,578 CpG sites Due to the small number of patients involved, only genes which had at least two significant CpGs were considered as “candidate” biomarker genes. This yielded 187 genes (389 CpGs)
When Benjamini–Hochberg correction applied, original no. of associated CpGs fell from 2870 (approximately 10%) to 30
20687937 Bell 2010 Blood DKD (n = 96) T1DM Irish 27 K array 27,578 CpG sites Over 400 differentially methylated CpG sites found (263 conferred increased risk and 162 conferred decreased risk for DKD)
Narrowed down to 19 CpGs when more stringent FDR threshold (0.05) applied
Many genes overlap with Ko et al. (2013) at less stringent threshold, but only one (RUNX3) when FDR threshold reduced to 0.05
  1. AUH: AU RNA binding methylglutaconyl-CoA hydratase; CKD: chronic kidney disease; CpGs: CpG islands or CG islands (5′—C—phosphate—G—3′: cytosine and guanine separated by only one phosphate group); DKD: diabetic kidney disease; DM: diabetes mellitus; DMRs: differentially methylated regions; MSP-HELP: methylation-sensitive and -insensitive isoschizomer enzymes (HpaII and MspI) followed by (HpaII) fragment enrichment by ligation-mediated PCR; HT: hypertension; RRT: renal replacement therapy; T1DM: type 1 diabetes mellitus; PMPCB: peptidase, mitochondrial processing beta subunit; RUNX3: runt related transcription factor 3; TSFM: Ts translation elongation factor; mitochondrial