Steinberg Julia, Shah Karan M, Gartland Alison, Zeggini Eleftheria, Wilkinson Jeremy Mark
Wellcome Trust Sanger Institute, Cambridge, UK.
Department of Oncology and Metabolism, The Mellanby Centre for Bone Research, The University of Sheffield, Sheffield, UK.
J Orthop Res. 2017 Oct;35(10):2323-2328. doi: 10.1002/jor.23525. Epub 2017 Feb 9.
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.
金属对金属（MOM）髋关节表面置换术近来已成为治疗症状性关节炎的一种常用假体选择，但该手术会导致钴和铬离子释放到循环系统中，这可能与不良临床效应相关。这些效应背后的机制仍不清楚。虽然染色体非整倍性和易位与这种暴露有关，但MOM关节置换患者中细微的结构表观遗传修饰情况仍未得到探索。因此，我们使用全基因组Illumina HumanMethylation 450k BeadChip芯片，分析了34例接受MOM髋关节表面置换术（MOM HR）的骨关节炎（OA）患者以及34例接受非MOM全髋关节置换术（非MOM THR）的OA患者的全血DNA甲基化情况。没有探针显示在5%错误发现率（FDR）水平上存在显著的差异甲基化。我们还直接测试了探针甲基化水平与血液中铬和钴水平的关联；在5% FDR水平上没有显著关联。最后，我们使用“表观遗传时钟”来比较所有个体样本的估计年龄与实际年龄。我们发现MOM HR组和非MOM THR组之间没有显著差异，年龄加速与血液金属水平也没有相关性。我们的结果表明，金属暴露后全身不存在大的甲基化差异，然而，需要更大的样本量来识别潜在的微小效应。假体周围局部组织中可能发生的任何DNA甲基化变化仍有待阐明。© 2017作者。骨科研究协会。由Wiley Periodicals, Inc.代表骨科研究协会出版。《骨科研究杂志》35:2323 - 2328, 2017年。
