DNA methylation profile associated with rapid decline in kidney function: findings from the CRIC Study
Year: 2014
Type: article
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.
DOI: 10.1093/ndt/gft537
Authors: M. R. Wing, J. M. Devaney, M. M. Joffe, D. Xie, H. I. Feldman, E. A. Dominic, N. J. Guzman, A. Ramezani, K. Susztak, J. G. Herman, L. Cope, B. Harmon, B. Kwabi-Addo, H. Gordish-Dressman, A. S. Go, J. He, J. P. Lash, J. W. Kusek, D. S. Raj, for the Chronic Renal Insufficiency Cohort (CRIC) Study
Institutions: George Washington University, Children's National, University of Pennsylvania, Albert Einstein College of Medicine, Johns Hopkins University, Johns Hopkins Medicine, Sidney Kimmel Comprehensive Cancer Center, Howard University, Kaiser Permanente, Kaiser Permanente Northern California, Tulane University, University of Illinois Chicago, National Institutes of Health, National Institute of Diabetes and Digestive and Kidney Diseases
Language: English
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: bronze
Awards: G1060671437, Gut Microbiota and Atherosclerosis in ESRD, G1201304535, G1226570316, G130883262, G1309951042, G1510223207, Clinical and Translational Science Institute, G1965526657, G2063336705, Case Western Reserve University/Cleveland Clinic CTSA (UL1), G239052087, Institute for Clinical and Translational Research (UL1), G2503904646, Continuation of the Chronic Renal Insufficiency Cohort (CRIC) Study, G2558937349, G269128772, G3195811987, G3209031725, G3428294221, G3771679604, G4070558115, G4177401362, G4727739888, Anti-inflammatory Therapy in Diabetic CKD, G483408255, G536099884, Epigenetic drivers and biomarkers of diabetic kidney disease, G606245974, G631514055, G751309980, G82803878, General Clinical Research Center, Clinical and Translational Science Collaborative of Cleveland, G9000035636, G9000036570, G9000037440, G9000118786, G9000141709, G9000162720, G9000270023, A pilot trial of an intervention to support initial type 2 diabetes selfmanagement among younger adults with children., Prospective renal insufficiency cohort evaluation: PRICE, Continuation of the University of Illinois Chicago CRIC Clinical Center, Tulane Clinical Center for Chronic Renal Insufficiency Cohort Study, Chronic Renal Insufficiency Cohort (CRIC) Study, G992700738
OpenAlex ID: W2105314711