{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,11]],"date-time":"2026-03-11T03:46:42Z","timestamp":1773200802353,"version":"3.50.1"},"reference-count":32,"publisher":"Wiley","issue":"11","license":[{"start":{"date-parts":[[2020,6,1]],"date-time":"2020-06-01T00:00:00Z","timestamp":1590969600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100003725","name":"National Research Foundation of Korea","doi-asserted-by":"publisher","award":["NRF\u20102017R1A2B4006767"],"award-info":[{"award-number":["NRF\u20102017R1A2B4006767"]}],"id":[{"id":"10.13039\/501100003725","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003725","name":"National Research Foundation of Korea","doi-asserted-by":"publisher","award":["NRF\u20102016M3A9B6026775"],"award-info":[{"award-number":["NRF\u20102016M3A9B6026775"]}],"id":[{"id":"10.13039\/501100003725","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004082","name":"Korean Foundation for Cancer Research","doi-asserted-by":"publisher","award":["KFCR\u20102017\u2010D\u20102"],"award-info":[{"award-number":["KFCR\u20102017\u2010D\u20102"]}],"id":[{"id":"10.13039\/501100004082","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Brit J Clinical Pharma"],"published-print":{"date-parts":[[2020,11]]},"abstract":"<jats:sec><jats:title>Aims<\/jats:title><jats:p>This study explores the effects of various genetic polymorphisms in candidate genes on thiopurine metabolism and toxicity in adult patients with Crohn's disease in Korea.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>A total of 131 adult patients with Crohn's disease receiving thiopurine treatment were included. The <jats:italic>TPMT<\/jats:italic> and <jats:italic>NUDT15<\/jats:italic> genes and an additional 116 genetic polymorphisms (in 40 genes and 3 intergenic locations) were screened for genotyping. Among the polymorphisms screened, 91 genetic polymorphisms (in 34 genes and 3 intergenic locations) in addition to <jats:italic>TPMT<\/jats:italic> and <jats:italic>NUDT15<\/jats:italic> genotypes were included for statistical analyses to investigate their effects on thiopurine metabolites and adverse outcomes (leukopenia, hepatotoxicity, gastrointestinal intolerance, skin rash and alopecia).<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>The median duration of thiopurine treatment was 47.0 months (range 6.0\u2013153.4 months). Patient sex, maintenance dose of thiopurine, and use of anti\u2010tumour necrosis factor agents were associated with thiopurine metabolite concentrations (<jats:italic>P<\/jats:italic> &lt; .05). In the univariate analysis, the <jats:italic>TPMT<\/jats:italic> genotype was associated with 6\u2010thioguanine level (<jats:italic>P<\/jats:italic> &lt; .05), although the significance of this did not remain in multivariate analysis. Genetic polymorphisms in the <jats:italic>ATIC<\/jats:italic> (rs3821353 and rs16853834), <jats:italic>IMPDH2<\/jats:italic> (rs11706052) and <jats:italic>ITPA<\/jats:italic> (rs6139036) genes were associated with thiopurine metabolism (<jats:italic>P<\/jats:italic> &lt; .05). Genetic polymorphisms in the <jats:italic>ABCC5<\/jats:italic> (rs8180093) and <jats:italic>NUDT15<\/jats:italic> genotypes were associated with leukopenia (<jats:italic>P<\/jats:italic> &lt; .05).<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>The results of this study may help clinicians to understand the effects of other various polymorphisms in addition to <jats:italic>TPMT<\/jats:italic> and <jats:italic>NUDP15<\/jats:italic> in thiopurine metabolism for management of Crohn's disease patients.<\/jats:p><\/jats:sec>","DOI":"10.1111\/bcp.14339","type":"journal-article","created":{"date-parts":[[2020,5,6]],"date-time":"2020-05-06T06:20:06Z","timestamp":1588746006000},"page":"2302-2313","source":"Crossref","is-referenced-by-count":15,"title":["Effects of various genetic polymorphisms on thiopurine treatment\u2010associated outcomes for Korean patients with Crohn's disease"],"prefix":"10.1111","volume":"86","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8266-2248","authenticated-orcid":false,"given":"Rihwa","family":"Choi","sequence":"first","affiliation":[{"name":"Department of Laboratory Medicine and Genetics, Samsung Medical Center Sungkyunkwan University School of Medicine  Seoul Republic of Korea"},{"name":"Department of Laboratory Medicine Green Cross Laboratories  Yongin Gyeonggi Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9923-264X","authenticated-orcid":false,"given":"Mi\u2010Na","family":"Lee","sequence":"additional","affiliation":[{"name":"Department of Laboratory Medicine Green Cross Laboratories  Yongin Gyeonggi Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0865-2236","authenticated-orcid":false,"given":"Kyunga","family":"Kim","sequence":"additional","affiliation":[{"name":"Statistics and Data 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