DNA methylation profile associated with rapid decline in kidney function: findings from the CRIC study

Nephrol Dial Transplant. 2014 Apr;29(4):864-72. doi: 10.1093/ndt/gft537. Epub 2014 Feb 9.

Abstract

Background: Epigenetic mechanisms may be important in the progression of chronic kidney disease (CKD).

Methods: We studied the genome-wide DNA methylation pattern associated with rapid loss of kidney function using the Infinium HumanMethylation 450 K BeadChip in 40 Chronic Renal Insufficiency (CRIC) study participants (n = 3939) with the highest and lowest rates of decline in estimated glomerular filtration rate.

Results: The mean eGFR slope was 2.2 (1.4) and -5.1 (1.2) mL/min/1.73 m(2) in the stable kidney function group and the rapid progression group, respectively. CpG islands in NPHP4, IQSEC1 and TCF3 were hypermethylated to a larger extent in subjects with stable kidney function (P-values of 7.8E-05 to 9.5E-05). These genes are involved in pathways known to promote the epithelial to mesenchymal transition and renal fibrosis. Other CKD-related genes that were differentially methylated are NOS3, NFKBIL2, CLU, NFKBIB, TGFB3 and TGFBI, which are involved in oxidative stress and inflammatory pathways (P-values of 4.5E-03 to 0.046). Pathway analysis using Ingenuity Pathway Analysis showed that gene networks related to cell signaling, carbohydrate metabolism and human behavior are epigenetically regulated in CKD.

Conclusions: Epigenetic modifications may be important in determining the rate of loss of kidney function in patients with established CKD.

Keywords: DNA methylation; chronic renal disease; chronic renal disease progression; epigenetics.

Publication types

  • Multicenter Study
  • Observational Study
  • Research Support, N.I.H., Extramural

MeSH terms

  • Adult
  • Aged
  • DNA Methylation / genetics*
  • Disease Progression
  • Epigenesis, Genetic*
  • Epithelial-Mesenchymal Transition
  • Female
  • Glomerular Filtration Rate*
  • Humans
  • Male
  • Middle Aged
  • Prognosis
  • Renal Insufficiency, Chronic / genetics*
  • Renal Insufficiency, Chronic / metabolism
  • Renal Insufficiency, Chronic / physiopathology
  • Young Adult

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