{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,3]],"date-time":"2026-09-03T18:01:00Z","timestamp":1788458460904,"version":"build-2803163510"},"reference-count":24,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2021,8,23]],"date-time":"2021-08-23T00:00:00Z","timestamp":1629676800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/100007172","name":"Cincinnati Children's Hospital Medical Center","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100007172","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["ascpt.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Clinical Translational Sci"],"published-print":{"date-parts":[[2022,1]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Low\u2010dose methotrexate (MTX) is an immunosuppressant used to treat inflammatory bowel disease (IBD). <jats:italic>SLCO1B1<\/jats:italic> genetic variation has been associated with delayed MTX clearance and increased toxicity. The purpose of this study was to evaluate the association between <jats:italic>SLCO1B1<\/jats:italic> genetic variation and MTX\u2010induced nausea in children with IBD. We performed a single center retrospective chart analysis of 278 patients who were prescribed MTX for IBD. Two hundred two patients had banked DNA and were genotyped for three <jats:italic>SLCO1B1<\/jats:italic> single nucleotide polymorphisms (SNPs; rs4149056, rs2306283, and rs11045819). Diplotypes were determined by combining the SNPs into *1, *4, *5, *14, *15, and *37 alleles. Incidence of nausea was abstracted from clinician notes. Prescriptions and demographics were extracted from the medical record. The cohort was 69.8% boys, 89.1% White, and 87.6% had a diagnosis of Crohn\u2019s disease with a mean age of 16.0 (\u00b1 3.8) years. MTX\u2010induced nausea was noted in 34% of the cohort. MTX\u2010induced nausea was associated with the number of reduced\u2010function *15 alleles (<jats:italic>p\u00a0<\/jats:italic>=\u00a00.034) and occurred 2.26 times more often in patients with at least one *15 allele who did not initiate MTX treatment with concomitant ondansetron (<jats:italic>p\u00a0<\/jats:italic>=\u00a00.034). MTX\u2010induced nausea was significantly independently associated with <jats:italic>SLCO1B1<\/jats:italic> diplotype (<jats:italic>p\u00a0<\/jats:italic>=\u00a00.006) after controlling for MTX dose group and concomitant ondansetron. Our data demonstrate that the <jats:italic>SLCO1B1<\/jats:italic> *15 allele is associated with MTX\u2010induced nausea in pediatric patients with IBD. Additionally, *15 allele carriers could benefit from a dose reduction of MTX to reduce exposure and treatment initiation with concomitant ondansetron to reduce nausea.<\/jats:p>","DOI":"10.1111\/cts.13130","type":"journal-article","created":{"date-parts":[[2021,8,23]],"date-time":"2021-08-23T13:15:14Z","timestamp":1629724514000},"page":"63-69","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":13,"title":["<i>SLCO1B1<\/i> *15 allele is associated with methotrexate\u2010induced nausea in pediatric patients with inflammatory bowel disease"],"prefix":"10.1111","volume":"15","author":[{"given":"Rishi S.","family":"Mehta","sequence":"first","affiliation":[{"name":"Division of Research in Patient Services Cincinnati Children\u2019s Hospital Medical Center  Cincinnati Ohio USA"},{"name":"Division of Clinical Pharmacology Cincinnati Children\u2019s Hospital Medical Center  Cincinnati Ohio USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5178-2397","authenticated-orcid":false,"given":"Zachary L.","family":"Taylor","sequence":"additional","affiliation":[{"name":"Division of Research in Patient Services Cincinnati Children\u2019s Hospital Medical Center  Cincinnati Ohio USA"},{"name":"Division of Clinical Pharmacology Cincinnati Children\u2019s Hospital Medical Center  Cincinnati Ohio USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8702-9946","authenticated-orcid":false,"given":"Lisa J.","family":"Martin","sequence":"additional","affiliation":[{"name":"Division of Human Genetics Cincinnati Children\u2019s Hospital Medical Center  Cincinnati Ohio USA"},{"name":"Department of Pediatrics University of Cincinnati College of Medicine  Cincinnati Ohio USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5149-718X","authenticated-orcid":false,"given":"Michael J.","family":"Rosen","sequence":"additional","affiliation":[{"name":"Division of Gastroenterology, Hepatology and Nutrition Cincinnati Children\u2019s Hospital Medical Center  Cincinnati Ohio USA"},{"name":"Department of Pediatrics University of Cincinnati College of Medicine  Cincinnati Ohio USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6417-3961","authenticated-orcid":false,"given":"Laura B.","family":"Ramsey","sequence":"additional","affiliation":[{"name":"Division of Research in Patient Services Cincinnati Children\u2019s Hospital Medical Center  Cincinnati Ohio USA"},{"name":"Division of Clinical Pharmacology Cincinnati Children\u2019s Hospital Medical Center  Cincinnati Ohio USA"},{"name":"Department of Pediatrics University of Cincinnati College of Medicine  Cincinnati 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of methotrexate intolerance in rheumatoid arthritis and psoriatic arthritis","volume":"15","author":"\u0106alasan MB","year":"2013","journal-title":"Arthritis Res Ther"},{"key":"e_1_2_9_17_1","doi-asserted-by":"publisher","DOI":"10.1097\/MIB.0000000000001014"},{"key":"e_1_2_9_18_1","doi-asserted-by":"publisher","DOI":"10.4065\/71.1.69"},{"key":"e_1_2_9_19_1","doi-asserted-by":"publisher","DOI":"10.1093\/ecco-jcc\/jjv027"},{"key":"e_1_2_9_20_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00296-016-3621-1"},{"key":"e_1_2_9_21_1","doi-asserted-by":"publisher","DOI":"10.1097\/MPG.0b013e31822855e7"},{"key":"e_1_2_9_22_1","doi-asserted-by":"crossref","DOI":"10.1186\/s12969-017-0180-2","article-title":"Methotrexate\u2010induced nausea in the treatment of juvenile idiopathic arthritis","volume":"15","author":"Falvey S","year":"2017","journal-title":"Pediatr. 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