Steinberg, J., Shah, K.M., Gartland, A. orcid.org/0000-0002-3712-2437 et al. (2 more authors) (2017) The effects of chronic cobalt and chromium exposure after metal-on-metal hip resurfacing: An epigenome-wide association pilot study. Journal of Orthopaedic Research. ISSN 0736-0266
Abstract
Metal-on-metal (MOM) hip resurfacing has recently been a popular prosthesis choice for the treatment of symptomatic arthritis, but results in the release of cobalt and chromium ions into the circulation that can be associated with adverse clinical effects. The mechanism underlying these effects remains unclear. While chromosomal aneuploidy and translocations are associated with this exposure, the presence of subtle structural epigenetic modifications in patients with MOM joint-replacements remains unexplored. Consequently, we analysed whole blood DNA methylation in 34 OA patients with MOM hip resurfacing (MOM HR) compared to 34 OA patients with non-MOM total hip replacements (non-MOM THR), using the genome-wide Illumina HumanMethylation 450k BeadChip. No probes showed differential methylation significant at 5% false-discovery rate (FDR). We also tested association of probe methylation levels with blood chromium and cobalt levels directly; there were no significant associations at 5% FDR. Finally, we used the 'epigenetic clock' to compare estimated to actual age at sample for all individuals. We found no significant difference between MOM HR and non-MOM THR, and no correlation of age acceleration with blood metal levels. Our results suggest the absence of large methylation differences systemically following metal exposure, however, larger sample sizes will be required to identify potential small effects. Any DNA methylation changes that may occur in the local periprosthetic tissues remain to be elucidated. This article is protected by copyright. All rights reserved.
Metadata
Item Type: | Article |
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Authors/Creators: |
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Copyright, Publisher and Additional Information: | This is the peer reviewed version of the following article: Steinberg, J., Shah, K. M., Gartland, A., Zeggini, E., & Wilkinson, J. M. (2017). The effects of chronic cobalt and chromium exposure after metal‐on‐metal hip resurfacing: An epigenome‐wide association pilot study. Journal of Orthopaedic Research, which has been published in final form at http://doi.org/10.1002/jor.23525. This article may be used for non-commercial purposes in accordance with Wiley Terms and Conditions for Self-Archiving. |
Keywords: | Chromium; Cobalt; DNA methylation; Metal-on-metal prostheses |
Dates: |
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Institution: | The University of Sheffield |
Academic Units: | The University of Sheffield > Faculty of Medicine, Dentistry and Health (Sheffield) > The Medical School (Sheffield) > Division of Genomic Medicine (Sheffield) > Department of Oncology and Metabolism (Sheffield) The University of Sheffield > Sheffield Teaching Hospitals |
Funding Information: | Funder Grant number ORTHOPAEDIC RESEARCH UK UNSPECIFIED |
Depositing User: | Symplectic Sheffield |
Date Deposited: | 31 Jan 2017 13:18 |
Last Modified: | 18 Jan 2018 01:38 |
Published Version: | http://doi.org/10.1002/jor.23525 |
Status: | Published |
Publisher: | Wiley |
Refereed: | Yes |
Identification Number: | 10.1002/jor.23525 |
Related URLs: | |
Open Archives Initiative ID (OAI ID): | oai:eprints.whiterose.ac.uk:110856 |