title: Effects of chronic cobalt and chromium exposure after metal-on-metal hip resurfacing: An epigenome-wide association pilot study.
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 analyzed 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. © 2017 The Authors. Orthopaedic Research Society. Published by Wiley Periodicals, Inc. on behalf of Orthopaedic Research Society. J Orthop Res 35:2323-2328, 2017.
authors.affiliation: Wellcome Trust Sanger Institute, Cambridge, UK.
authors.forename: Julia
authors.initials: J
authors.lastname: Steinberg
authors.affiliation: Department of Oncology and Metabolism, The Mellanby Centre for Bone Research, The University of Sheffield, Sheffield, UK.
authors.forename: Karan M
authors.initials: KM
authors.lastname: Shah
authors.affiliation: Department of Oncology and Metabolism, The Mellanby Centre for Bone Research, The University of Sheffield, Sheffield, UK.
authors.forename: Alison
authors.initials: A
authors.lastname: Gartland
authors.affiliation: Wellcome Trust Sanger Institute, Cambridge, UK.
authors.forename: Eleftheria
authors.initials: E
authors.lastname: Zeggini
authors.affiliation: Department of Oncology and Metabolism, The Mellanby Centre for Bone Research, The University of Sheffield, Sheffield, UK.
authors.forename: Jeremy Mark
authors.initials: JM
authors.lastname: Wilkinson
mesh_terms: D000368:Aged; D016022:Case-Control Studies; D002857:Chromium / Q000009:adverse effects*; D003035:Cobalt / Q000009:adverse effects*; D019175:DNA Methylation; D057890:Epigenomics; D005260:Female; D006622:Hip Prosthesis / Q000009:adverse effects*; D006801:Humans; D008297:Male; D008875:Middle Aged; D010865:Pilot Projects
chemical_list: D002857:Chromium; D003035:Cobalt
keywords: DNA methylation; chromium; cobalt; metal-on-metal prostheses