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Immunol. Ther. Exp."],"published-print":{"date-parts":[[2020,8]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Inconsistency of the results regarding the genetic variability within genes coding for receptor activator of nuclear factor \u03baB (RANK) and its ligand (RANKL) in rheumatoid arthritis (RA) prompted us to study the <jats:italic>RANK<\/jats:italic> and <jats:italic>RANKL<\/jats:italic> polymorphisms as potential biomarkers associated with disease predisposition and response to anti-TNF treatment in a group of Polish patients with RA. This study enrolled 318 RA patients and 163 controls. <jats:italic>RANK<\/jats:italic> (rs8086340, C\u2009&gt;\u2009G; rs1805034, C\u2009&gt;\u2009T) and <jats:italic>RANKL<\/jats:italic> (rs7325635, G\u2009&gt;\u2009A; rs7988338 G\u2009&gt;\u2009A) alleles were determined by real-time PCR with melting curve analysis and related with clinical parameters. In addition, RANKL serum levels were measured by ELISA. The <jats:italic>RANK<\/jats:italic> rs8086340-<jats:italic>G<\/jats:italic> allele was overrepresented among patients as compared to controls (OD\u2009=\u20091.777, <jats:italic>p<\/jats:italic>\u2009=\u20090.038). C-reactive protein (CRP) levels were significantly (<jats:italic>p<\/jats:italic>\u2009&lt;\u20090.05) associated with <jats:italic>RANK<\/jats:italic> rs8086340 polymorphism and were higher in the <jats:italic>CC<\/jats:italic>-homozygotes at the baseline while lower in the <jats:italic>GG<\/jats:italic>-carriers at the 12th week of the treatment. At the latter time point <jats:italic>RANKL<\/jats:italic> rs7325635-<jats:italic>GG-<\/jats:italic>positive patients also showed significantly lower CRP concentrations. Higher alkaline phosphatase levels before induction of anti-TNF therapy were observed in <jats:italic>RANK<\/jats:italic> rs8086340 and <jats:italic>RANK<\/jats:italic> rs1805034 <jats:italic>CC<\/jats:italic> homozygotes (<jats:italic>p<\/jats:italic>\u2009=\u20090.057 and <jats:italic>p<\/jats:italic>\u2009=\u20090.035, respectively). The <jats:italic>GG<\/jats:italic> homozygosity of both <jats:italic>RANKL<\/jats:italic> single nucleotide polymorphisms was significantly associated with the number of swollen joints (rs7988338 and rs7325635, before and at the 12th week of therapy, respectively, <jats:italic>p<\/jats:italic>\u2009&lt;\u20090.05 in both cases). These results imply that polymorphisms within the <jats:italic>RANK<\/jats:italic> and <jats:italic>RANKL<\/jats:italic> genes affect RA susceptibility and anti-TNF treatment outcome.<\/jats:p>","DOI":"10.1007\/s00005-020-00590-6","type":"journal-article","created":{"date-parts":[[2020,8,19]],"date-time":"2020-08-19T19:03:36Z","timestamp":1597863816000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":14,"title":["Polymorphisms within the RANK and RANKL Encoding Genes in Patients with Rheumatoid Arthritis: Association with Disease Progression and Effectiveness of the Biological Treatment"],"prefix":"10.2478","volume":"68","author":[{"given":"Joanna","family":"Wieli\u0144ska","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katarzyna","family":"Kolossa","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jerzy","family":"\u015awierkot","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marta","family":"Dratwa","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Milena","family":"Iwaszko","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bartosz","family":"Bugaj","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Barbara","family":"Wysocza\u0144ska","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Monika","family":"Chaszczewska-Markowska","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"S\u0142awomir","family":"Jeka","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9744-0376","authenticated-orcid":false,"given":"Katarzyna","family":"Bogunia-Kubik","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"374","published-online":{"date-parts":[[2020,8,19]]},"reference":[{"key":"590_CR1","doi-asserted-by":"crossref","first-page":"900","DOI":"10.3899\/jrheum.091110","volume":"37","author":"G Assmann","year":"2010","unstructured":"Assmann G, Koenig J, Pfreundschuh M et al (2010) Genetic variations in genes encoding RANK, RANKL, and OPG in rheumatoid arthritis: a case-control study. 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