{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T19:07:04Z","timestamp":1791313624405,"version":"4.3.1"},"reference-count":37,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2022,9,11]],"date-time":"2022-09-11T00:00:00Z","timestamp":1662854400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100002858","name":"China Postdoctoral Science Foundation","doi-asserted-by":"publisher","award":["2020M683139"],"award-info":[{"award-number":["2020M683139"]}],"id":[{"id":"10.13039\/501100002858","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["ascpt.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Clin Pharma and Therapeutics"],"published-print":{"date-parts":[[2022,12]]},"abstract":"<jats:p>Thiopurine dose optimization by thiopurine\u2010S\u2010methyltransferase (<jats:italic>TPMT<\/jats:italic>) or nudix hydrolase\u201015 (<jats:italic>NUDT15<\/jats:italic>) significantly reduced early leucopenia in Asia. However, it fails to avoid the late incidence (&gt;\u20092\u2009months). Although laboratory monitoring of 6\u2010thioguanine nucleotides (6TGN) to optimize thiopurine dose was suggested in White patients the exact association between leucopenia and 6TGN was controversial in Asian patients. In the present study, we aimed to explore whether DNA\u2010thioguanine nucleotides (DNA\u2010TGs) in leukocytes, compared with 6TGN in erythrocytes, can be a better biomarker for late leucopenia. This was a prospective, observational study. Patients with inflammatory bowel disease (IBD) prescribed thiopurine from February 2019 to December 2019 were recruited. Thiopurine dose was optimized by <jats:italic>NUDT15<\/jats:italic> C415T (rs116855232). DNA\u2010TG and 6TGN levels were determined at the time of late leucopenia or 2\u2009months after the stable dose was obtained. A total of 308 patients were included. Thiopurine induced late leucopenia (white blood cells\u2009&lt;\u20093.5\u2009\u00d7\u200910<jats:sup>9<\/jats:sup>\/L) were observed in 43 patients (14.0%), who had significantly higher DNA\u2010TG concentration than those without leucopenia (<jats:italic>P<\/jats:italic>\u00a0= 4.1\u2009\u00d7\u200910<jats:sup>\u20139<\/jats:sup>, 423.3 (~\u2009342.2\u2009to\u2009565.7) vs. 270.5 (~\u2009188.1\u2009to\u2009394.3) fmol\/\u03bcg DNA). No difference in 6TGN concentrations between leucopenia and non\u2010leucopenia was found. With a DNA\u2010TG threshold of 340.1\u2009fmol\/\u03bcg DNA, 83.7% of leucopenia cases could be identified. Multivariate analysis showed that DNA\u2010TG was an independent risk factor for late leucopenia. Quantification of DNA\u2010TG, rather than 6TGN, can be applied to gauge thiopurine therapy after <jats:italic>NUDT15<\/jats:italic> screening in Chinese patients with IBD.<\/jats:p>","DOI":"10.1002\/cpt.2730","type":"journal-article","created":{"date-parts":[[2022,8,25]],"date-time":"2022-08-25T02:14:45Z","timestamp":1661393685000},"page":"1236-1242","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":12,"title":["<scp>DNA<\/scp>\u2010Thioguanine Nucleotides as a Marker for Thiopurine Induced Late Leukopenia after Dose Optimizing by <scp><i>NUDT15<\/i> C415T<\/scp> in Chinese Patients with <scp>IBD<\/scp>"],"prefix":"10.1111","volume":"112","author":[{"given":"Xia","family":"Zhu","sequence":"first","affiliation":[{"name":"Department of Gastroenterology, The Sixth Affiliated Hospital Sun Yat\u2010sen University  Guangzhou China"},{"name":"Guangdong Provincial Key Laboratory of New Drug Design and Evaluation, School of Pharmaceutical Sciences Sun Yat\u2010sen University  Guangzhou China"},{"name":"Guangdong Institute of Gastroenterology Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Diseases, Supported by National Key Clinical Discipline  Guangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kang","family":"Chao","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology, The Sixth Affiliated Hospital Sun Yat\u2010sen University  Guangzhou China"},{"name":"Guangdong Institute of Gastroenterology Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Diseases, Supported by National Key Clinical Discipline  Guangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ting","family":"Yang","sequence":"additional","affiliation":[{"name":"Guangdong Provincial Key Laboratory of New Drug Design and Evaluation, School of Pharmaceutical Sciences Sun Yat\u2010sen University  Guangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xue\u2010ding","family":"Wang","sequence":"additional","affiliation":[{"name":"Guangdong Provincial Key Laboratory of New Drug Design and Evaluation, School of Pharmaceutical Sciences Sun Yat\u2010sen University  Guangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shaoxing","family":"Guan","sequence":"additional","affiliation":[{"name":"Guangdong Provincial Key Laboratory of New Drug Design and Evaluation, School of Pharmaceutical Sciences Sun Yat\u2010sen University  Guangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jian","family":"Tang","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology, The Sixth Affiliated Hospital Sun Yat\u2010sen University  Guangzhou China"},{"name":"Guangdong Institute of Gastroenterology Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Diseases, Supported by National Key Clinical Discipline  Guangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wen","family":"Xie","sequence":"additional","affiliation":[{"name":"Center for Pharmacogenetics and Department of Pharmaceutical Sciences University of Pittsburgh  Pittsburgh Pennsylvania USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ai\u2010ming","family":"Yu","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Molecular Medicine UC Davis School of Medicine  Sacramento California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qing fan","family":"Yang","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology, The Sixth Affiliated Hospital Sun Yat\u2010sen University  Guangzhou China"},{"name":"Guangdong Institute of Gastroenterology Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Diseases, Supported by National Key Clinical Discipline  Guangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Miao","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology, The Sixth Affiliated Hospital Sun Yat\u2010sen University  Guangzhou China"},{"name":"Guangdong Institute of Gastroenterology Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Diseases, Supported by National Key Clinical Discipline  Guangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hong\u2010sheng","family":"Yang","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology, The Sixth Affiliated Hospital Sun Yat\u2010sen University  Guangzhou China"},{"name":"Guangdong Institute of Gastroenterology Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Diseases, Supported by National Key Clinical Discipline  Guangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Na","family":"Diao","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology, The Sixth Affiliated Hospital Sun Yat\u2010sen University  Guangzhou China"},{"name":"Guangdong Institute of Gastroenterology Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Diseases, Supported by National Key Clinical Discipline  Guangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pin\u2010jin","family":"Hu","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology, The Sixth Affiliated Hospital Sun Yat\u2010sen University  Guangzhou China"},{"name":"Guangdong Institute of Gastroenterology Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Diseases, Supported by National Key Clinical Discipline  Guangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3058-4655","authenticated-orcid":false,"given":"Xiang","family":"Gao","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology, The Sixth Affiliated Hospital Sun Yat\u2010sen University  Guangzhou China"},{"name":"Guangdong Institute of Gastroenterology Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Diseases, Supported by National Key Clinical Discipline  Guangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Min","family":"Huang","sequence":"additional","affiliation":[{"name":"Guangdong Provincial Key Laboratory of New Drug Design and Evaluation, School of Pharmaceutical Sciences Sun Yat\u2010sen University  Guangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2022,9,11]]},"reference":[{"key":"e_1_2_8_1_1","doi-asserted-by":"publisher","DOI":"10.1093\/ecco-jcc\/jjx181"},{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1002\/ibd.21221"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1111\/apt.13559"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cgh.2009.07.019"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.3389\/fphar.2018.01107"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.1002\/cpt.1304"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.1093\/gastro\/goaa021"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.1111\/apt.13796"},{"key":"e_1_2_8_9_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng.3060"},{"key":"e_1_2_8_10_1","doi-asserted-by":"publisher","DOI":"10.1038\/tpj.2015.43"},{"key":"e_1_2_8_11_1","doi-asserted-by":"publisher","DOI":"10.1111\/apt.16600"},{"key":"e_1_2_8_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cgh.2019.08.034"},{"key":"e_1_2_8_13_1","doi-asserted-by":"publisher","DOI":"10.1111\/apt.15403"},{"key":"e_1_2_8_14_1","doi-asserted-by":"publisher","DOI":"10.3748\/wjg.v25.i38.5850"},{"key":"e_1_2_8_15_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00535-015-1142-4"},{"key":"e_1_2_8_16_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrc2292"},{"key":"e_1_2_8_17_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng.3508"},{"key":"e_1_2_8_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jchromb.2016.06.017"},{"key":"e_1_2_8_19_1","doi-asserted-by":"publisher","DOI":"10.1111\/jgh.14465"},{"key":"e_1_2_8_20_1","doi-asserted-by":"publisher","DOI":"10.1097\/MIB.0000000000001148"},{"key":"e_1_2_8_21_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.crohns.2014.08.009"},{"key":"e_1_2_8_22_1","doi-asserted-by":"publisher","DOI":"10.1097\/01.ftd.0000169061.52715.3e"},{"key":"e_1_2_8_23_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00535-021-01820-0"},{"key":"e_1_2_8_24_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1470-2045(17)30154-7"},{"key":"e_1_2_8_25_1","doi-asserted-by":"publisher","DOI":"10.1139\/y96-056"},{"key":"e_1_2_8_26_1","doi-asserted-by":"publisher","DOI":"10.1053\/j.gastro.2017.07.032"},{"key":"e_1_2_8_27_1","doi-asserted-by":"publisher","DOI":"10.1097\/FPC.0000000000000282"},{"key":"e_1_2_8_28_1","doi-asserted-by":"publisher","DOI":"10.1002\/cpt.1268"},{"key":"e_1_2_8_29_1","doi-asserted-by":"publisher","DOI":"10.1111\/apt.15458"},{"key":"e_1_2_8_30_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00535-018-1486-7"},{"key":"e_1_2_8_31_1","doi-asserted-by":"publisher","DOI":"10.1002\/cpt.2716"},{"key":"e_1_2_8_32_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41397-021-00255-3"},{"key":"e_1_2_8_33_1","first-page":"1664","article-title":"ITPA genotyping is not predictive for the development of side effects in AZA treated inflammatory bowel disease patients","volume":"54","author":"Dieren J.M.","year":"2005","journal-title":"Gut"},{"key":"e_1_2_8_34_1","doi-asserted-by":"publisher","DOI":"10.3389\/fped.2021.719803"},{"key":"e_1_2_8_35_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00535-010-0248-y"},{"key":"e_1_2_8_36_1","doi-asserted-by":"publisher","DOI":"10.1080\/17425255.2021.1974398"},{"key":"e_1_2_8_37_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1915680117"}],"container-title":["Clinical Pharmacology &amp; Therapeutics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/cpt.2730","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/cpt.2730","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/ascpt.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/cpt.2730","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,11,7]],"date-time":"2023-11-07T13:37:15Z","timestamp":1699364235000},"score":1,"resource":{"primary":{"URL":"https:\/\/ascpt.onlinelibrary.wiley.com\/doi\/10.1002\/cpt.2730"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,9,11]]},"references-count":37,"journal-issue":{"issue":"6","published-print":{"date-parts":[[2022,12]]}},"alternative-id":["10.1002\/cpt.2730"],"URL":"https:\/\/doi.org\/10.1002\/cpt.2730","archive":["Portico"],"relation":{},"ISSN":["0009-9236","1532-6535"],"issn-type":[{"value":"0009-9236","type":"print"},{"value":"1532-6535","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,9,11]]},"assertion":[{"value":"2022-05-16","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2022-08-15","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2022-09-11","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}