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 |