{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,5]],"date-time":"2026-05-05T10:46:11Z","timestamp":1777977971548,"version":"3.51.4"},"reference-count":49,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2014,4,9]],"date-time":"2014-04-09T00:00:00Z","timestamp":1397001600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"name":"NKTH (National Research and Technology)","award":["TECH_08-A1\/2-2008-0120"],"award-info":[{"award-number":["TECH_08-A1\/2-2008-0120"]}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Br J Haematol"],"published-print":{"date-parts":[[2014,8]]},"abstract":"<jats:title>Summary<\/jats:title><jats:p>High\u2010dose methotrexate (<jats:styled-content style=\"fixed-case\">HD<\/jats:styled-content>\u2010<jats:styled-content style=\"fixed-case\">MTX<\/jats:styled-content>) plays an important role in the consolidation therapy of acute lymphoblastic leukaemia (<jats:styled-content style=\"fixed-case\">ALL<\/jats:styled-content>) in many treatment regimens worldwide. However, there is a large interpatient variability in the pharmacokinetics and toxicity of the drug. We investigated the influence of single nucleotide polymorphisms (<jats:styled-content style=\"fixed-case\">SNP<\/jats:styled-content>s) in genes of the folate metabolic pathway, transporter molecules and transcription proteins on the pharmacokinetics and toxicity of <jats:styled-content style=\"fixed-case\">MTX<\/jats:styled-content> and 7\u2010hydroxy\u2010methotrexate (7\u2010<jats:styled-content style=\"fixed-case\">OH<\/jats:styled-content>\u2010<jats:styled-content style=\"fixed-case\">MTX<\/jats:styled-content>). 63 <jats:styled-content style=\"fixed-case\">SNP<\/jats:styled-content>s of 14 genes were genotyped and a total of 463 <jats:styled-content style=\"fixed-case\">HD<\/jats:styled-content>\u2010<jats:styled-content style=\"fixed-case\">MTX<\/jats:styled-content> courses (administered according to the <jats:styled-content style=\"fixed-case\">ALL<\/jats:styled-content>\u2010<jats:styled-content style=\"fixed-case\">BFM<\/jats:styled-content> 95 and <jats:styled-content style=\"fixed-case\">ALL IC<\/jats:styled-content>\u2010<jats:styled-content style=\"fixed-case\">BFM<\/jats:styled-content> 2002 protocols) were analysed. Haematological, hepatic and renal toxicities, estimated by routine laboratory parameters were evaluated. Random forest and regression trees were used for variable selection and model building. Linear mixed models were established to prove the significance of the selected variables. <jats:styled-content style=\"fixed-case\">SNP<\/jats:styled-content>s (rs4948502, rs4948496, rs4948487) of the <jats:italic><jats:styled-content style=\"fixed-case\">ARID<\/jats:styled-content>5<jats:styled-content style=\"fixed-case\">B<\/jats:styled-content><\/jats:italic> gene were associated with the serum levels of <jats:styled-content style=\"fixed-case\">MTX<\/jats:styled-content> (<jats:italic>P<\/jats:italic>\u00a0&lt;\u00a00\u00b702), serum levels and area under the curve of 7\u2010<jats:styled-content style=\"fixed-case\">OH<\/jats:styled-content>\u2010<jats:styled-content style=\"fixed-case\">MTX<\/jats:styled-content> (<jats:italic>P<\/jats:italic>\u00a0&lt;\u00a00\u00b702) and with hypoproteinaemia (<jats:italic>P<\/jats:italic>\u00a0=\u00a00\u00b7004). <jats:italic><jats:styled-content style=\"fixed-case\">SLCO<\/jats:styled-content>1B1<\/jats:italic> rs4149056 also showed a significant association with serum <jats:styled-content style=\"fixed-case\">MTX<\/jats:styled-content> levels (<jats:italic>P<\/jats:italic>\u00a0&lt;\u00a00\u00b7001). Our findings confirm the association of novel genetic variations in folate\u2010related and <jats:italic><jats:styled-content style=\"fixed-case\">ARID<\/jats:styled-content>5B<\/jats:italic> genes with the serum <jats:styled-content style=\"fixed-case\">MTX<\/jats:styled-content> levels and acute toxicity.<\/jats:p>","DOI":"10.1111\/bjh.12886","type":"journal-article","created":{"date-parts":[[2014,4,9]],"date-time":"2014-04-09T07:27:38Z","timestamp":1397028458000},"page":"410-420","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":38,"title":["Associations of novel genetic variations in the folate\u2010related and <i><scp>ARID<\/scp>5<scp>B<\/scp><\/i> genes with the pharmacokinetics and toxicity of high\u2010dose methotrexate in paediatric acute lymphoblastic leukaemia"],"prefix":"10.1111","volume":"166","author":[{"given":"Katalin","family":"Csordas","sequence":"first","affiliation":[{"name":"2nd Department of Paediatrics Semmelweis University Budapest Hungary"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Orsolya","family":"Lautner\u2010Csorba","sequence":"additional","affiliation":[{"name":"Deparment of Genetics, Cell\u2010 and Immunbiology Semmelweis University Budapest Hungary"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Agnes F.","family":"Semsei","sequence":"additional","affiliation":[{"name":"Deparment of Genetics, Cell\u2010 and Immunbiology Semmelweis University Budapest Hungary"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Andrea","family":"Harnos","sequence":"additional","affiliation":[{"name":"Department of Biomathematics and Informatics Faculty of Veterinary Science Szent Istvan University Budapest Hungary"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marta","family":"Hegyi","sequence":"additional","affiliation":[{"name":"2nd Department of Paediatrics Semmelweis University Budapest Hungary"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Daniel J.","family":"Erdelyi","sequence":"additional","affiliation":[{"name":"2nd Department of Paediatrics Semmelweis University Budapest Hungary"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Oliver T.","family":"Eipel","sequence":"additional","affiliation":[{"name":"2nd Department of Paediatrics Semmelweis University Budapest Hungary"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Csaba","family":"Szalai","sequence":"additional","affiliation":[{"name":"Deparment of Genetics, Cell\u2010 and Immunbiology Semmelweis University Budapest Hungary"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gabor T.","family":"Kovacs","sequence":"additional","affiliation":[{"name":"2nd Department of Paediatrics Semmelweis University Budapest Hungary"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2014,4,9]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1002\/0471249688"},{"key":"e_1_2_9_3_1","volume-title":"A Randomized Trial of the I\u2010BFM\u2010SG for the Management of Childhood Non\u2010B Acute Lymphoblastic Leukemia Final Version of Therapy Protocol from May 3, 2002","author":"ALL IC\u2010BFM Trial Steering Committee","year":"2002"},{"key":"e_1_2_9_4_1","unstructured":"ALL IC\u2010BFM Trial Steering Committee(2009)A Randomized Trial of the I\u2010BFM\u2010SG for the Management of Childhood Non\u2010B Acute Lymphoblastic Leukemia. 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