DNA hypermethylation and DNA hypomethylation is present at different loci in chronic kidney disease

Figures & data

Figure 1. The impact of epigenetics for chronic kidney disease. A role for epigenetics for chronic kidney disease.

Table 1. Top-ranked 23 genes showing most significant differences in methylation status between case and control groups

Symbol	Description	Number of top ranked CpGs and features	Potential role	Top-ranked CpG	Cytogenetic location	P value (delta β)	Function and processes by gene ontology
ANKRD11	ankyrin repeat domain 11	Three; 5′UTR, north and south shelves	Encoded protein inhibits ligand-dependent activation of transcription. Mutations associated with syndromes, including renal dysfunction.	cg26957471	16q24.3	3.67E-12 (0.03)	Development and homeostasis
BANP	BTG3 associated nuclear protein	Three; 5′UTR, CpG island, body and north shelf	Encoded protein binds to matrix attachment regions	cg07018090	16q24	1.70E-10 (-0.36)	DNA binding, Cell cycle, chromatin modification, transcription
BRD2	bromodomain containing 2	Three; genic	Located within the MHC region, this gene encodes a transcriptional regulator that associates with transcription complexes and with acetylated chromatin during mitosis, and it selectively binds to the acetylated lysine-12 residue of histone H4	cg01716683	6p21.3	4.68E-10 (0.09)	Chromatin binding and modification, transcription, nucleosome assembly
CRISPLD2	cysteine-rich secretory protein LCCL domain containing 2	Two; enhancer	Not evident	cg01704698	16q24.1	1.53E-09 (0.2)	Extracellular matrix organization, heparin binding
CUX1	cut-like homeobox 1	Two; body, south shore, Promoter associated	Involved with kidney development and dysfunction. May regulate gene expression, morphogenesis, and differentiation, and it may also play a role in the cell cycle progression	cg02858808	7q22.1	3.67E-09 (0.05)	Chromatin binding, DNA binding, differentiation, transcription
DCUN1D2	DCN1, defective in cullin neddylation 1, domain containing 2 (S. cerevisiae)	Two; genic	Upregulated in animal model of transplantation following administration of a methyltransferase inhibitor	cg02128308	13q34	1.11E-09 (0.06)	Induces cell-growth arrest
ELMO1	engulfment and cell motility 1	Two; Enhancer	Encodes a member of the engulfment and cell motility protein family and has been associated with diabetic kidney disease	cg08044454	7p14.1	2.74E-09 (-0.2)	Protein binding, actin cytoskeleton organization, protein signal transduction, cellular component movement and apoptotic process
EXOC3	exocyst complex component 3	Two; body, island	Interacts with the actin cytoskeletal remodeling and vesicle transport machinery	cg17500228	5p15.33	1.57E-14 (0.3)	Protein binding, exocytosis, protein transport
FKBP5	FK506 binding protein 5	Three; 5′UTR, TSS1500, north and south shores, enhancer, promoter associated	Role in immunoregulation and basic cellular processes involving protein folding and trafficking. Mediates calcineurin inhibition	cg00130530	6p21.31	3.33E-10 (-0.09)	Heat shock protein binding, FK506 binding, protein folding, isomerization
GALNT2	UDP-N-acetyl-α-D-galactosamine:polypeptide N-acetylgalactosaminyltransferase 2 (GalNAc-T2)	Two; Enhancer, Promoter Associated	Member of the GalNAc-transferases family and associated with cholesterol	cg23843953	1q41-q42	1.10E-10 (0.08)	Glycan processing, cellular metabolism, protein modification, immunoglobulin biosynthetic process
IFLTD1	intermediate filament tail domain containing 1	Two; genic	Not evident	cg13134916	12p12.1	2.27E-10 (0.2)	Cell proliferation
INHBA-AS1	INHBA antisense RNA 1	Two; body, south shore, enhancer	Long non-coding antisense RNA potentially involved in kidney damage and transplant rejection	cg26478599	7p14.1	2.90E-11 (0.3)
JARID2	jumonji, AT rich interactive domain 2	Three; enhancer	DNA-binding protein that functions as a transcriptional repressor. Associated with blood pressure and cholesterol	cg12230983	6p24-p23	8.47E-18 (0.1)	DNA binding, chromatin binding, development, cell proliferation, histone methylation, transcription, differentiation
MCM2	minichromosome maintenance complex component 2	Two; body, island, enhancer	Highly conserved mini-chromosome maintenance proteins (MCM) that are involved in the initiation of eukaryotic genome replication. Prognositic marker for kidney cancer	cg13296238	3q21	5.03E-11 (0.1)	ATP binding, DNA binding, replication, histone binding, cell cycle
PRKAG2	protein kinase, AMP-activated, gamma 2 non-catalytic subunit	Two; enhancer	Component of an important energy-sensing enzyme that monitors cellular energy status and functions by inactivating key enzymes involved in regulating de novo biosynthesis of fatty acid and cholesterol. Associated with CKD	cg10370262	7q36.1	3.67E-09 (0.08)	ATP binding, protein kinase activity, metabolic processes, insulin signaling,
PTPRN2	protein tyrosine phosphatase, receptor type, N polypeptide 2	Two; body, north shore	Major autoantigen associated with insulin-dependent diabetes mellitus. Associated with CKD	cg24701780	7q36	8.87E-10 (0.02)	Transmembrane receptor protein tyrosine phosphatase activity, GTPase activity, protein dephosphorylation
SLC6A16	solute carrier family 6, member 16	Two; TSS200, island	Not evident	cg00041047	19q13.33	8.33E-11 (-0.2)	Neurotransmitter transport and activity
STK24	serine/threonine kinase 24	Two; enhancer	Not evident	cg07804470	13q31.2-q32.3	1.50E-10 (0.2)	ATP binding, metal ion binding, protein binding, protein kinase activity, apoptosis, regulation of cell migration, phosphorylation, signal transduction
SYNPO2	synaptopodin 2	Two; enhancer	Not evident	cg13541713	4q26	7.53E-11 (0.2)	14–3-3 protein binding, actin binding
TP53BP2	tumor protein p53 binding protein, 2	Two; Enhancer, Promoter Associated	Regulates apoptosis and cell growth through interactions with other regulatory molecules	cg03992323	1q41	2.10E-09 (0.2)	NFkB binding, SH3 domain binding, SH3/SH2 adaptor activity, protein binding, apoptosis, cell cycle, development, signal transduction
VPS52	vacuolar protein sorting 52 homolog (S. cerevisiae)	Three; body, south shelf and shore	Involved in vesicle trafficking	cg26987613	6p21.3	1.50E-14 (0.1)	Protein binding, protein transport
WDR46	WD repeat domain 46	Two; body, north shore	Not evident	cg16458752	6p21.3	8.13E-10 (0.05)	Molecular function, biological process
ZFP36L1	zinc finger protein 36, C3H type-like 1	Three; body, island, promoter associated	Putative nuclear transcription factor most likely functions in regulating the response to growth factors.Congenital anomalies of the kidney and urinary tract gene	cg08169020	14q22-q24	5.23E-10 (-0.3)	DNA, RNA, transcription factor, and protein binding, differentiation, gene expression, metabolic processes, regulation of mRNA stability, transcription and translation, vasculogenesis

Delta β is positive for increased methylation in cases and negative for decreased methylation between case and control groups.

Figure 2. Location of key features for genes that are strong biological candidates for kidney disease including CUX1, ELMO1, FKBP5, INHBA-AS1, PTPRN2, and PRKAG2.