{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T03:02:40Z","timestamp":1787022160139,"version":"build-2736575974"},"reference-count":65,"publisher":"Public Library of Science (PLoS)","issue":"5","license":[{"start":{"date-parts":[[2025,5,15]],"date-time":"2025-05-15T00:00:00Z","timestamp":1747267200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"the Rush Scientific Leadership Council through the Searle Innovators Award"},{"name":"the National Institutes of Health (NIH), National Institute of Arthritis Musculoskeletal and Skin","award":["T32AR073157"],"award-info":[{"award-number":["T32AR073157"]}]}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS One"],"abstract":"<jats:p>As the number of patients undergoing total joint replacement (TJR) surgery increases, so does the number of revision surgeries. One driver of implant failure and subsequent revision surgery is peri-implant osteolysis, which is driven by inflammation-mediated bone loss. IL-6 is an inflammatory cytokine that is elevated during the peri-operative period. Early elevations in IL-6 levels have been linked to osteolysis development. The current study asked whether there is genetic contribution to the IL-6-related peri-operative inflammatory reaction to TJR surgery. Patients undergoing primary TJR (total hip or total knee) provided pre-operative and post-operative blood samples for measurement of the circulating levels of IL-6 and the soluble IL-6 receptor (sIL-6r), as well as evaluation of allele status of three single nucleotide polymorphisms (SNPs) linked to IL-6 or sIL-6r levels - rs2069845, rs2228145, and rs4537545. Circulating sIL-6r levels were associated with allele status in the rs2228145 SNP. More interestingly, allele status in the rs2069845 SNP was associated with the change in circulating IL-6 levels following TJR surgery. Specifically, patients with the A,A allele had increasing levels of IL-6, while those harboring the G,A allele had decreasing levels of IL-6. While implant survival was not assessed, the critical role of IL-6 in peri-implant osteolysis suggests that the rs2069845 allele may influence orthopedic implant success. rs2069845 polymorphisms may be a useful patient-specific marker of inflammatory response to TJR surgery.<\/jats:p>","DOI":"10.1371\/journal.pone.0312985","type":"journal-article","created":{"date-parts":[[2025,5,15]],"date-time":"2025-05-15T13:41:14Z","timestamp":1747316474000},"page":"e0312985","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":1,"title":["Polymorphisms in rs2069845 are associated with IL-6 and soluble IL-6 receptor levels during total joint replacement"],"prefix":"10.1371","volume":"20","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5312-7801","authenticated-orcid":true,"given":"Kyle 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