title: DNA methylation profile associated with rapid decline in kidney function: findings from the CRIC study.
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.
authors: Division of Renal Diseases and Hypertension, The George Washington University School of Medicine, Washington, DC, USA.
authors: Maria R
authors: MR
authors: Wing
authors: Joseph M
authors: JM
authors: Devaney
authors: Marshall M
authors: MM
authors: Joffe
authors: Dawei
authors: D
authors: Xie
authors: Harold I
authors: HI
authors: Feldman
authors: Elizabeth A
authors: EA
authors: Dominic
authors: Nicolas J
authors: NJ
authors: Guzman
authors: Ali
authors: A
authors: Ramezani
authors: Katalin
authors: K
authors: Susztak
authors: James G
authors: JG
authors: Herman
authors: Leslie
authors: L
authors: Cope
authors: Brennan
authors: B
authors: Harmon
authors: Bernard
authors: B
authors: Kwabi-Addo
authors: Heather
authors: H
authors: Gordish-Dressman
authors: Alan S
authors: AS
authors: Go
authors: Jiang
authors: J
authors: He
authors: James P
authors: JP
authors: Lash
authors: John W
authors: JW
authors: Kusek
authors: Dominic S
authors: DS
authors: Raj
mesh_terms: D000328:Adult; D000368:Aged; D019175:DNA Methylation / Q000235:genetics*; D018450:Disease Progression; D044127:Epigenesis, Genetic; D058750:Epithelial-Mesenchymal Transition; D005260:Female; D005919:Glomerular Filtration Rate; D006801:Humans; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D051436:Renal Insufficiency, Chronic / Q000235:genetics* / Q000378:metabolism / Q000503:physiopathology; D055815:Young Adult
keywords: DNA methylation; chronic renal disease; chronic renal disease progression; epigenetics