Polymorphisms in rs2069845 are associated with IL-6 and soluble IL-6 receptor levels during total joint replacement.

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 cytoki...

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Main Authors: Kyle D Anderson, Bryan Dulion, John Wong, Niyati Patel, Anne DeBenedetti, Craig J Della Valle, Ryan D Ross
Format: Article
Language:English
Published: Public Library of Science (PLoS) 2025-01-01
Series:PLoS ONE
Online Access:https://doi.org/10.1371/journal.pone.0312985
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author Kyle D Anderson
Bryan Dulion
John Wong
Niyati Patel
Anne DeBenedetti
Craig J Della Valle
Ryan D Ross
author_facet Kyle D Anderson
Bryan Dulion
John Wong
Niyati Patel
Anne DeBenedetti
Craig J Della Valle
Ryan D Ross
author_sort Kyle D Anderson
collection DOAJ
description 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.
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spelling doaj-art-5bc691b6c8f94bbcbfab2ea1a5f745ba2025-08-20T03:47:28ZengPublic Library of Science (PLoS)PLoS ONE1932-62032025-01-01205e031298510.1371/journal.pone.0312985Polymorphisms in rs2069845 are associated with IL-6 and soluble IL-6 receptor levels during total joint replacement.Kyle D AndersonBryan DulionJohn WongNiyati PatelAnne DeBenedettiCraig J Della ValleRyan D RossAs 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.https://doi.org/10.1371/journal.pone.0312985
spellingShingle Kyle D Anderson
Bryan Dulion
John Wong
Niyati Patel
Anne DeBenedetti
Craig J Della Valle
Ryan D Ross
Polymorphisms in rs2069845 are associated with IL-6 and soluble IL-6 receptor levels during total joint replacement.
PLoS ONE
title Polymorphisms in rs2069845 are associated with IL-6 and soluble IL-6 receptor levels during total joint replacement.
title_full Polymorphisms in rs2069845 are associated with IL-6 and soluble IL-6 receptor levels during total joint replacement.
title_fullStr Polymorphisms in rs2069845 are associated with IL-6 and soluble IL-6 receptor levels during total joint replacement.
title_full_unstemmed Polymorphisms in rs2069845 are associated with IL-6 and soluble IL-6 receptor levels during total joint replacement.
title_short Polymorphisms in rs2069845 are associated with IL-6 and soluble IL-6 receptor levels during total joint replacement.
title_sort polymorphisms in rs2069845 are associated with il 6 and soluble il 6 receptor levels during total joint replacement
url https://doi.org/10.1371/journal.pone.0312985
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