{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T16:42:31Z","timestamp":1791304951422,"version":"4.3.1"},"reference-count":44,"publisher":"Wiley","issue":"10","license":[{"start":{"date-parts":[[2008,9,29]],"date-time":"2008-09-29T00:00:00Z","timestamp":1222646400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Arthritis &amp; Rheumatism"],"published-print":{"date-parts":[[2008,10]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Objective<\/jats:title><jats:p>To determine whether osteolysis after total hip arthroplasty (THA) is associated with common polymorphisms within the genes encoding the interleukin\u20101 (IL\u20101) family and IL\u20106, and to determine whether polymorphisms that are associated with osteolysis affect in vitro messenger RNA (mRNA) expression in human peripheral blood mononuclear cells (PBMCs) in response to wear particles.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Unrelated white subjects of North European descent (n = 612) were recruited a mean of 11 years after cemented THA for primary osteoarthritis. Of these subjects, 272 had previous osteolysis and 340 had no radiographic evidence of osteolysis (control group). Genomic DNA was genotyped for the following single\u2010nucleotide polymorphisms (SNPs): <jats:italic>IL1A<\/jats:italic> +4845, <jats:italic>IL1B<\/jats:italic> +3954, <jats:italic>IL1B<\/jats:italic> \u20133737, <jats:italic>IL1B<\/jats:italic> \u2013511, <jats:italic>IL1RA<\/jats:italic> +2018, <jats:italic>IL6<\/jats:italic> \u2013174, <jats:italic>IL6<\/jats:italic> \u2013572, and <jats:italic>IL6<\/jats:italic> \u2013597. In a subset of 60 subjects, PBMCs were extracted and stimulated with titanium particles and\/or endotoxin, and cytokine mRNA expression was measured using quantitative real\u2010time reverse transcriptase\u2013polymerase chain reaction.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>The odds ratio (OR) for osteolysis associated with carriage of the <jats:italic>IL1RA<\/jats:italic> +2018C allele was 0.66 (95% confidence interval [95% CI] 0.48\u20130.91) (<jats:italic>P<\/jats:italic> = 0.012). The remaining SNPs were not individually associated with osteolysis. The uncommon <jats:italic>IL6<\/jats:italic> haplotype \u2212174G\/\u2212572G\/\u2212597A (osteolysis group frequency 2.4%, control group frequency 0.8%) was associated with osteolysis (<jats:italic>P<\/jats:italic> = 0.02, calculated using Haploview software). The <jats:italic>IL1RA<\/jats:italic> +2018CC genotype was associated with increased mRNA expression compared with the +2018TT genotype in both unstimulated and stimulated PBMCs (<jats:italic>P<\/jats:italic> = 0.01 by analysis of variance, after Bonferroni correction).<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>The <jats:italic>IL1RA<\/jats:italic> +2018C allele is associated with a decreased risk of osteolysis after THA and with increased IL\u20101 receptor antagonist mRNA expression in vitro. An uncommon haplotype within the promoter region of the gene for IL\u20106 is positively associated with osteolysis.<\/jats:p><\/jats:sec>","DOI":"10.1002\/art.23863","type":"journal-article","created":{"date-parts":[[2008,9,29]],"date-time":"2008-09-29T04:33:23Z","timestamp":1222662803000},"page":"3157-3165","source":"Crossref","is-referenced-by-count":58,"title":["Polymorphisms in the interleukin\u20101 receptor antagonist and interleukin\u20106 genes affect risk of osteolysis in patients with total hip arthroplasty"],"prefix":"10.1002","volume":"58","author":[{"given":"Andrew","family":"Gordon","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"E.","family":"Kiss\u2010Toth","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ian","family":"Stockley","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Richard","family":"Eastell","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J. 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