{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,24]],"date-time":"2026-09-24T20:06:04Z","timestamp":1790280364097,"version":"4.1.0"},"reference-count":36,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2021,3,29]],"date-time":"2021-03-29T00:00:00Z","timestamp":1616976000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100001411","name":"Indian Council of Medical Research","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100001411","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":[[2021,5]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Introduction<\/jats:title><jats:p>The adenosine pathway is one of the ways through which methotrexate (MTX) ameliorates inflammation. We therefore explored an association of polymorphism of genes involved in adenosine and MTX metabolic pathways with response to MTX.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Association of polymorphism in 7 genes (rs2236225 [<jats:italic>MTHFD1<\/jats:italic> 1958G&gt;A], rs17602729 [<jats:italic>AMPD1<\/jats:italic> G&gt;A], rs1127354 [<jats:italic>ITPA<\/jats:italic> C&gt;A], rs1431131 [<jats:italic>TGFBR2<\/jats:italic> A&gt;T], rs2372536 [<jats:italic>ATIC<\/jats:italic> C&gt;G], rs11188513 [<jats:italic>ENTPD1<\/jats:italic> C&gt;T] and rs5751876 [<jats:italic>ADORA2A<\/jats:italic> T&gt;C]) with efficacy of MTX was studied in Indian rheumatoid arthritis (RA) patients. The patients, classified by European League Against Rheumatology (EULAR)\/American College of Rheumatology (ACR) 2010 criteria, were DMARD (disease\u2010modifying antirheumatic drug)\u2010na\u00efve, with Disease Activity Score (DAS28) &gt;3.2. After 4\u00a0months of MTX monotherapy, patients were classified as responders (R) or non\u2010responders (NR) based on EULAR response criteria. Genotyping was done by TaqMan 5' nuclease assay and association of gene polymorphisms with response to MTX was determined by Chi\u2010squared test.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Two hundred and twenty\u2010six patients (86% female, median age 40 [interquartile range, IQR\u00a0=\u00a017.25] years), with disease duration of 24 (IQR\u00a0=\u00a038.25) months and DAS28\u2010C\u2010reactive protein score of 4.61 (IQR\u00a0=\u00a01.34) were enrolled. After therapy, 186 patients were classified as R and 40 as NR. GG genotype of <jats:italic>ATIC<\/jats:italic> (<jats:italic>P<\/jats:italic>\u00a0=\u00a0.01, odds ratio [OR] 2.56, 95% CI, 1.04\u20106.30) and CC genotype of <jats:italic>ITPA<\/jats:italic> (<jats:italic>P<\/jats:italic>\u00a0=\u00a0.009, OR 1.34, 95% CI 1.02\u20101.76) genes were found to be associated with the response. On binary logistic regression analysis, GG genotype of <jats:italic>ATIC<\/jats:italic> and CC of <jats:italic>ITPA<\/jats:italic> genes were independent predictors of the response.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Polymorphisms of <jats:italic>ATIC<\/jats:italic> and <jats:italic>ITPA<\/jats:italic> genes alone or with clinical variables were associated with response to MTX therapy in Indian RA patients.<\/jats:p><\/jats:sec>","DOI":"10.1111\/1756-185x.14100","type":"journal-article","created":{"date-parts":[[2021,3,29]],"date-time":"2021-03-29T12:24:23Z","timestamp":1617020663000},"page":"654-662","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Polymorphism of genes involved in methotrexate pathway: Predictors of response to methotrexate therapy in Indian rheumatoid arthritis 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