Longitudinal genome-wide DNA methylation changes in response to kidney failure replacement therapy

Witasp, A., Luttropp, K., Qureshi, A. R., Barany, P., Heimbürger, O., Wennberg, L., Ekström, T. J., Shiels, P. G. , Stenvinkel, P. and Nordfors, L. (2022) Longitudinal genome-wide DNA methylation changes in response to kidney failure replacement therapy. Scientific Reports, 12, 470. (doi: 10.1038/s41598-021-04321-5) (PMID:35013499) (PMCID:PMC8748627)

[img] Text
260945.pdf - Published Version
Available under License Creative Commons Attribution.

2MB

Abstract

Chronic kidney disease (CKD) is an emerging public health priority associated with high mortality rates and demanding treatment regimens, including life-style changes, medications or even dialysis or renal transplantation. Unavoidably, the uremic milieu disturbs homeostatic processes such as DNA methylation and other vital gene regulatory mechanisms. Here, we aimed to investigate how dialysis or kidney transplantation modifies the epigenome-wide methylation signature over 12 months of treatment. We used the Infinium HumanMethylation450 BeadChip on whole blood samples from CKD-patients undergoing either dialysis (n = 11) or kidney transplantation (n = 12) and 24 age- and sex-matched population-based controls. At baseline, comparison between patients and controls identified several significant (PFDR < 0.01) CpG methylation differences in genes with functions relevant to inflammation, cellular ageing and vascular calcification. Following 12 months, the global DNA methylation pattern of patients approached that seen in the control group. Notably, 413 CpG sites remained differentially methylated at follow-up in both treatment groups compared to controls. Together, these data indicate that the uremic milieu drives genome-wide methylation changes that are partially reversed with kidney failure replacement therapy. Differentially methylated CpG sites unaffected by treatment may be of particular interest as they could highlight candidate genes for kidney disease per se.

Item Type:Articles
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Shiels, Professor Paul
Authors: Witasp, A., Luttropp, K., Qureshi, A. R., Barany, P., Heimbürger, O., Wennberg, L., Ekström, T. J., Shiels, P. G., Stenvinkel, P., and Nordfors, L.
College/School:College of Medical Veterinary and Life Sciences > Institute of Cancer Sciences
Journal Name:Scientific Reports
Publisher:Nature Publishing Group
ISSN:2045-2322
ISSN (Online):2045-2322
Published Online:10 January 2022
Copyright Holders:Copyright © The Author(s) 2022
First Published:First published in Scientific Reports 2022
Publisher Policy:Reproduced under a Creative Commons licence

University Staff: Request a correction | Enlighten Editors: Update this record