{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T00:39:47Z","timestamp":1787013587751,"version":"build-2736575974"},"reference-count":42,"publisher":"Wiley","issue":"10","license":[{"start":{"date-parts":[[2018,8,13]],"date-time":"2018-08-13T00:00:00Z","timestamp":1534118400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The Journal of Dermatology"],"published-print":{"date-parts":[[2018,10]]},"abstract":"Abstract<\/jats:title>\n \n Azathioprine (\n AZA<\/jats:styled-content>\n )\u2010metabolizing enzyme gene polymorphism is strongly related to thiopurine\u2010induced leukocytopenia, which has not been well recognized in dermatological practice. We tried to see whether\n \n NUDT<\/jats:styled-content>\n 15\n <\/jats:italic>\n gene polymorphism can be the most susceptible genetic factor for\n AZA<\/jats:styled-content>\n toxicity and the gene screening is beneficial to avoid the adverse events of\n AZA<\/jats:styled-content>\n for the treatment of skin diseases. A retrospective study was carried out on 15 adult Japanese patients who were treated with\n AZA<\/jats:styled-content>\n . Gene polymorphism of thiopurine\u2010metabolizing enzymes\n \n NUDT<\/jats:styled-content>\n 15\n <\/jats:italic>\n R139C,\n \n ITPA<\/jats:styled-content>\n <\/jats:italic>\n 94C>A,\n \n TPMT<\/jats:styled-content>\n <\/jats:italic>\n *2,\n \n TPMT<\/jats:styled-content>\n <\/jats:italic>\n *3B and\n \n TPMT<\/jats:styled-content>\n <\/jats:italic>\n *3C was analyzed. The single nucleotide polymorphisms were prospectively investigated in eight patients who were considered to have received\n AZA<\/jats:styled-content>\n treatments. Two\n \n NUDT<\/jats:styled-content>\n 15\n <\/jats:italic>\n R139C homozygous patients developed agranulocytosis, severe thrombocytopenia and massive hair loss. The gene screening prior to\n AZA<\/jats:styled-content>\n treatment identified one heterozygote of\n \n NUDT<\/jats:styled-content>\n 15\n <\/jats:italic>\n R139C and\n \n ITPA<\/jats:styled-content>\n <\/jats:italic>\n 94C>A, and three heterozygotes of\n \n ITPA<\/jats:styled-content>\n <\/jats:italic>\n 94C>A or\n \n TMPT<\/jats:styled-content>\n <\/jats:italic>\n *3C. Although this study was a retrospective single\u2010center case\u2013control observational study that enrolled a small number of patients,\n \n NUDT<\/jats:styled-content>\n 15\n <\/jats:italic>\n R139C homozygosity is a genetic risk of thiopurine\u2010induced potentially fetal hematological abnormalities. To avoid serious adverse events, gene screening of thiopurine\u2010metabolizing enzymes, at least\n \n NUDT<\/jats:styled-content>\n 15\n <\/jats:italic>\n R139C, should be considered prior to administration in genetically predisposed populations, such as Japanese. We highlight that massive hair loss in the early period of the initiation of\n AZA<\/jats:styled-content>\n would be a sign of impending severe myelotoxicity.\n <\/jats:p>","DOI":"10.1111\/1346-8138.14588","type":"journal-article","created":{"date-parts":[[2018,8,13]],"date-time":"2018-08-13T06:15:25Z","timestamp":1534140925000},"page":"1160-1165","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":19,"title":["Severe thiopurine\u2010induced leukocytopenia and hair loss in Japanese patients with defective\n \n NUDT<\/scp>\n <\/i>\n 15 variant: Retrospective case\u2013control study"],"prefix":"10.1111","volume":"45","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2966-1756","authenticated-orcid":false,"given":"Mari","family":"Kishibe","sequence":"first","affiliation":[{"name":"Department of Dermatology Asahikawa Medical University Asahikawa Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6797-131X","authenticated-orcid":false,"given":"Hiroyoshi","family":"Nozaki","sequence":"additional","affiliation":[{"name":"Department of Dermatology Asahikawa Medical University Asahikawa Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2571-1071","authenticated-orcid":false,"given":"Mizue","family":"Fujii","sequence":"additional","affiliation":[{"name":"Department of Dermatology Asahikawa Medical University Asahikawa Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3673-0932","authenticated-orcid":false,"given":"Shin","family":"Iinuma","sequence":"additional","affiliation":[{"name":"Department of Dermatology Asahikawa Medical University Asahikawa Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sawa","family":"Ohtsubo","sequence":"additional","affiliation":[{"name":"Department of Dermatology Asahikawa Medical University Asahikawa Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Satomi","family":"Igawa","sequence":"additional","affiliation":[{"name":"Department of Dermatology Asahikawa Medical University Asahikawa Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3135-9254","authenticated-orcid":false,"given":"Kyoko","family":"Kanno","sequence":"additional","affiliation":[{"name":"Department of Dermatology Asahikawa Medical University Asahikawa Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1566-5331","authenticated-orcid":false,"given":"Masaru","family":"Honma","sequence":"additional","affiliation":[{"name":"Department of Dermatology Asahikawa Medical University Asahikawa Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kan","family":"Kishibe","sequence":"additional","affiliation":[{"name":"Department of Otorhinolaryngology Asahikawa Medical University Asahikawa Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kensaku","family":"Okamoto","sequence":"additional","affiliation":[{"name":"Division of Metabolism and Biosystemic Science Department of Medicine Asahikawa Medical University Asahikawa Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3104-102X","authenticated-orcid":false,"given":"Akemi","family":"Ishida\u2010Yamamoto","sequence":"additional","affiliation":[{"name":"Department of Dermatology Asahikawa Medical University Asahikawa Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2018,8,13]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1440-1746.2005.03832.x"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1001\/jamaoncol.2015.0245"},{"issue":"2","key":"e_1_2_7_4_1","first-page":"S105","article-title":"Renal transplantation, past, present and future","volume":"12","author":"Ponticelli C","year":"1999","journal-title":"J Nephrol"},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.2165\/00003495-199754040-00003"},{"key":"e_1_2_7_6_1","doi-asserted-by":"publisher","DOI":"10.1136\/annrheumdis-2013-204575"},{"key":"e_1_2_7_7_1","doi-asserted-by":"publisher","DOI":"10.1191\/096120301676669495"},{"key":"e_1_2_7_8_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa0802311"},{"key":"e_1_2_7_9_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1468-3083.2012.04717.x"},{"key":"e_1_2_7_10_1","doi-asserted-by":"publisher","DOI":"10.1001\/archderm.143.12.1536"},{"key":"e_1_2_7_11_1","doi-asserted-by":"publisher","DOI":"10.2174\/138161210790112773"},{"key":"e_1_2_7_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bcp.2010.01.006"},{"issue":"2","key":"e_1_2_7_13_1","doi-asserted-by":"crossref","first-page":"261","DOI":"10.15403\/jgld.2014.1121.252.nud","article-title":"NUDT15: a novel player in thiopurine metabolism","volume":"25","author":"Meijer B","year":"2016","journal-title":"J Gastrointestin Liver Dis"},{"key":"e_1_2_7_14_1","doi-asserted-by":"publisher","DOI":"10.1097\/FTD.0b013e3181dbd712"},{"key":"e_1_2_7_15_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2710.2011.01272.x"},{"key":"e_1_2_7_16_1","doi-asserted-by":"publisher","DOI":"10.1177\/0961203307085255"},{"key":"e_1_2_7_17_1","doi-asserted-by":"publisher","DOI":"10.7326\/0003-4819-154-12-201106210-00009"},{"key":"e_1_2_7_18_1","doi-asserted-by":"publisher","DOI":"10.1053\/j.gastro.2017.07.032"},{"key":"e_1_2_7_19_1","doi-asserted-by":"publisher","DOI":"10.18632\/oncotarget.14594"},{"key":"e_1_2_7_20_1","doi-asserted-by":"publisher","DOI":"10.1038\/clpt.2013.4"},{"key":"e_1_2_7_21_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12929-016-0291-y"},{"key":"e_1_2_7_22_1","doi-asserted-by":"publisher","DOI":"10.1097\/00008571-200403000-00006"},{"key":"e_1_2_7_23_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbadis.2006.10.006"},{"key":"e_1_2_7_24_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00535-008-2307-1"},{"key":"e_1_2_7_25_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng.3060"},{"key":"e_1_2_7_26_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng.3508"},{"key":"e_1_2_7_27_1","doi-asserted-by":"publisher","DOI":"10.1158\/0008-5472.CAN-16-0584"},{"key":"e_1_2_7_28_1","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/8.2.367"},{"key":"e_1_2_7_29_1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2014.59.4671"},{"key":"e_1_2_7_30_1","doi-asserted-by":"publisher","DOI":"10.5217\/ir.2017.15.3.328"},{"key":"e_1_2_7_31_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jns.2017.04.041"},{"key":"e_1_2_7_32_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00535-015-1142-4"},{"key":"e_1_2_7_33_1","doi-asserted-by":"publisher","DOI":"10.1038\/tpj.2015.43"},{"key":"e_1_2_7_34_1","doi-asserted-by":"publisher","DOI":"10.1111\/bjh.13518"},{"issue":"4","key":"e_1_2_7_35_1","doi-asserted-by":"crossref","first-page":"475","DOI":"10.1097\/MEG.0000000000000564","article-title":"NUDT15 variant is the most common variant associated with thiopurine\u2010induced early leukopenia and alopecia in Korean pediatric patients with Crohn's disease","volume":"28","author":"Lee YJ","year":"2016","journal-title":"Eur J Gastro Hepatol"},{"key":"e_1_2_7_36_1","doi-asserted-by":"publisher","DOI":"10.4103\/0378-6323.116728"},{"key":"e_1_2_7_37_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0190-9622(99)70488-3"},{"key":"e_1_2_7_38_1","doi-asserted-by":"publisher","DOI":"10.1093\/jnci\/91.23.2001"},{"key":"e_1_2_7_39_1","doi-asserted-by":"publisher","DOI":"10.1038\/clpt.2008.261"},{"key":"e_1_2_7_40_1","doi-asserted-by":"publisher","DOI":"10.2146\/ajhp120179"},{"key":"e_1_2_7_41_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00535-010-0248-y"},{"key":"e_1_2_7_42_1","doi-asserted-by":"publisher","DOI":"10.3324\/haematol.2015.134775"},{"key":"e_1_2_7_43_1","doi-asserted-by":"publisher","DOI":"10.1038\/tpj.2017.12"}],"container-title":["The Journal of Dermatology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1111%2F1346-8138.14588","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/1346-8138.14588","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,9,16]],"date-time":"2023-09-16T18:30:02Z","timestamp":1694889002000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/1346-8138.14588"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2018,8,13]]},"references-count":42,"journal-issue":{"issue":"10","published-print":{"date-parts":[[2018,10]]}},"alternative-id":["10.1111\/1346-8138.14588"],"URL":"https:\/\/doi.org\/10.1111\/1346-8138.14588","archive":["Portico"],"relation":{},"ISSN":["0385-2407","1346-8138"],"issn-type":[{"value":"0385-2407","type":"print"},{"value":"1346-8138","type":"electronic"}],"subject":[],"published":{"date-parts":[[2018,8,13]]},"assertion":[{"value":"2018-06-04","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2018-07-03","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2018-08-13","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}