{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,20]],"date-time":"2026-09-20T14:39:15Z","timestamp":1789915155325,"version":"4.0.1"},"reference-count":54,"publisher":"The Journal of Rheumatology","issue":"10","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["J Rheumatol"],"published-print":{"date-parts":[[2012,10]]},"abstract":"<jats:sec><jats:title>Objective.<\/jats:title><jats:p>Although methotrexate (MTX) is the most widely prescribed drug in juvenile idiopathic arthritis (JIA), 30% of patients fail to respond to it. To individualize treatment strategies, the genetic determinants of response to MTX should be identified.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods.<\/jats:title><jats:p>A cohort of 287 patients with JIA treated with MTX was studied longitudinally over the first year of treatment. MTX response was defined as the American College of Rheumatology pediatric 70 criteria (ACRped70). We genotyped 21 single-nucleotide polymorphisms in 13 genes related to MTX polyglutamylation and to cellular MTX uptake and efflux. Potential associations between ACRped70 and genotypes were analyzed in a multivariate model and corrected for these 3 covariates: disease duration prior to MTX treatment, physician\u2019s global assessment of disease activity at baseline, and MTX dose at all study visits.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results.<\/jats:title><jats:p>MTX response was more often achieved by patients variant for the adenosine triphosphate-binding cassette transporter B1 (<jats:italic>ABCB1<\/jats:italic>) gene polymorphism rs1045642 (OR 3.80, 95% CI 1.70\u22128.47, p = 0.001) and patients variant for the<jats:italic>ABCC3<\/jats:italic>gene polymorphism rs4793665 (OR 3.10, 95% CI 1.49\u22126.41, p = 0.002) than by patients with other genotypes. Patients variant for the solute carrier 19A1 (<jats:italic>SLC19A1<\/jats:italic>) gene polymorphism rs1051266 were less likely to respond to MTX (OR 0.25, 95% CI 0.09\u22120.72, p = 0.011).<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion.<\/jats:title><jats:p><jats:italic>ABCB1<\/jats:italic>rs1045642,<jats:italic>ABCC3<\/jats:italic>rs4793665, and<jats:italic>SLC19A1<\/jats:italic>rs1051266 polymorphisms were associated with response to MTX in 287 patients with JIA studied longitudinally. Upon validation of our results in other JIA cohorts, these genetic determinants may help to individualize treatment strategies by predicting clinical response to MTX.<\/jats:p><\/jats:sec>","DOI":"10.3899\/jrheum.111593","type":"journal-article","created":{"date-parts":[[2012,8,2]],"date-time":"2012-08-02T05:29:34Z","timestamp":1343885374000},"page":"2032-2040","source":"Crossref","is-referenced-by-count":66,"title":["<i>ABCB1<\/i>and<i>ABCC3<\/i>Gene Polymorphisms Are Associated with First-year Response to Methotrexate in Juvenile Idiopathic Arthritis"],"prefix":"10.3899","volume":"39","author":[{"given":"MAURITS C.F.J.","family":"de ROTTE","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"MAJA","family":"BULATOVIC","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"MARLOES W.","family":"HEIJSTEK","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"GERRIT","family":"JANSEN","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"SANDRA G.","family":"HEIL","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"RON H.N.","family":"van SCHAIK","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"NICO M.","family":"WULFFRAAT","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"ROBERT","family":"de JONGE","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"2262","published-online":{"date-parts":[[2012,8,1]]},"reference":[{"key":"2018112909282082000_39.10.2032.1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(07)60363-8"},{"key":"2018112909282082000_39.10.2032.2","doi-asserted-by":"publisher","DOI":"10.1002\/art.20288"},{"key":"2018112909282082000_39.10.2032.3","doi-asserted-by":"publisher","DOI":"10.1038\/ncprheum0380"},{"key":"2018112909282082000_39.10.2032.4","doi-asserted-by":"publisher","DOI":"10.1016\/j.drup.2006.09.001"},{"key":"2018112909282082000_39.10.2032.5","doi-asserted-by":"publisher","DOI":"10.1136\/ard.2004.033399"},{"key":"2018112909282082000_39.10.2032.6","doi-asserted-by":"publisher","DOI":"10.1002\/art.22129"},{"key":"2018112909282082000_39.10.2032.7","first-page":"313","article-title":"Methotrexate polyglutamate levels in circulating erythrocytes and polymorphs correlate with clinical efficacy in rheumatoid arthritis","volume":"17","author":"Angelis-Stoforidis","year":"1999","journal-title":"Clin Exp Rheumatol"},{"key":"2018112909282082000_39.10.2032.8","doi-asserted-by":"publisher","DOI":"10.1002\/art.20460"},{"key":"2018112909282082000_39.10.2032.9","doi-asserted-by":"publisher","DOI":"10.1097\/00008571-200411000-00004"},{"key":"2018112909282082000_39.10.2032.10","doi-asserted-by":"publisher","DOI":"10.1038\/nrrheum.2011.117"},{"key":"2018112909282082000_39.10.2032.11","first-page":"1832","article-title":"Influence of methylenetetrahydrofolate reductase polymorphisms on efficacy and toxicity of methotrexate in patients with juvenile idiopathic arthritis","volume":"32","author":"Schmeling","year":"2005","journal-title":"J Rheumatol"},{"key":"2018112909282082000_39.10.2032.12","doi-asserted-by":"publisher","DOI":"10.1002\/art.24087"},{"key":"2018112909282082000_39.10.2032.13","doi-asserted-by":"publisher","DOI":"10.1136\/ard.2010.146191"},{"key":"2018112909282082000_39.10.2032.14","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2125.2010.03814.x"},{"key":"2018112909282082000_39.10.2032.15","doi-asserted-by":"publisher","DOI":"10.1002\/art.30080"},{"key":"2018112909282082000_39.10.2032.16","doi-asserted-by":"publisher","DOI":"10.3899\/jrheum.091427"},{"key":"2018112909282082000_39.10.2032.17","doi-asserted-by":"publisher","DOI":"10.1097\/FPC.0b013e32833f2cd0"},{"key":"2018112909282082000_39.10.2032.18","first-page":"390","article-title":"International League of Associations for Rheumatology classification of juvenile idiopathic arthritis: second revision, Edmonton, 2001","volume":"31","author":"Petty","year":"2004","journal-title":"J Rheumatol"},{"key":"2018112909282082000_39.10.2032.19","doi-asserted-by":"publisher","DOI":"10.1002\/1529-0131(199707)40:7<1202::AID-ART3>3.0.CO;2-R"},{"key":"2018112909282082000_39.10.2032.20","unstructured":"International Hapmap Project . 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