{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,30]],"date-time":"2025-10-30T22:43:00Z","timestamp":1761864180817,"version":"3.40.5"},"reference-count":30,"publisher":"Wiley","issue":"11","license":[{"start":{"date-parts":[[2020,9,23]],"date-time":"2020-09-23T00:00:00Z","timestamp":1600819200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100014841","name":"Medac","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100014841","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100005888","name":"Uniwersytet Medyczny w Lodzi","doi-asserted-by":"publisher","award":["502\u201003\/8\u2010000\u201004\/502\u201064\u2010114\u201019"],"award-info":[{"award-number":["502\u201003\/8\u2010000\u201004\/502\u201064\u2010114\u201019"]}],"id":[{"id":"10.13039\/501100005888","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Int J of Rheum Dis"],"published-print":{"date-parts":[[2020,11]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Aim<\/jats:title><jats:p>Methotrexate (MTX) administered at the dose 10\u201015\u00a0mg\/m<jats:sup>2<\/jats:sup> is recommended as the first\u2010line therapy in most juvenile idiopathic arthritis (JIA) subtypes. The disease\u2010modifying effect of methotrexate is associated with release of adenosine and mediated via binding to adenosine receptor A2A (ADORA2A) and 3 (ADORA3). The aim of our study was to determine the association between single nucleotide polymorphisms in <jats:italic>ADORA2A<\/jats:italic> (rs2236624, rs2298383) and <jats:italic>ADORA3<\/jats:italic> (rs3393) receptor genes on the disease activity and presence of MTX therapy side effects in patients with JIA.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>One hundred children with JIA of all subtypes treated with MTX were recruited to the study. Demographic and clinical parameters were collected at the baseline of MTX therapy and on a control visit 4\u20106\u00a0months after starting MTX. Single nucleotide polymorphism genotyping was performed using genomic DNA isolated from peripheral blood samples.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>The polymorphic variant of <jats:italic>ADORA2A<\/jats:italic> rs2236624 was associated with ~3.5 times higher odds of gastrointestinal side effects occurrence (odds ratio: 3.59, 95% CI: 1.15\u201011.22, <jats:italic>P<\/jats:italic>\u00a0=\u00a00.0282). Children with the <jats:italic>ADORA3<\/jats:italic> rs3393 polymorphic variants (CT\/CC) after 6\u00a0months of MTX treatment had significantly lower number of joints with active arthritis (median: 0.00 vs 1.00, <jats:italic>P<\/jats:italic>\u00a0=\u00a00.0400) and value of C\u2010reactive protein (0.60 vs 2.40, <jats:italic>P<\/jats:italic>\u00a0=\u00a00.0242) in comparison to TT variant.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Although future studies are needed to verify our findings, polymorphisms in <jats:italic>ADORA2A<\/jats:italic> and <jats:italic>ADORA3<\/jats:italic> genes may become the determinants of MTX treatment efficacy and gastrointestinal toxicity in children with JIA.<\/jats:p><\/jats:sec>","DOI":"10.1111\/1756-185x.13972","type":"journal-article","created":{"date-parts":[[2020,9,24]],"date-time":"2020-09-24T07:53:57Z","timestamp":1600934037000},"page":"1505-1513","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["The impact of single nucleotide polymorphisms in <i>ADORA2A<\/i> and <i>ADORA3<\/i> genes on the early response to methotrexate and presence of therapy side effects in children with juvenile idiopathic arthritis: Results of a preliminary study"],"prefix":"10.1111","volume":"23","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1487-7156","authenticated-orcid":false,"given":"Justyna","family":"Roszkiewicz","sequence":"first","affiliation":[{"name":"Department of Paediatric Cardiology and Rheumatology Medical University of Lodz  Lodz 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