{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,25]],"date-time":"2026-10-25T00:14:58Z","timestamp":1792887298670,"version":"4.5.0"},"reference-count":32,"publisher":"Oxford University Press (OUP)","issue":"12","license":[{"start":{"date-parts":[[2023,6,22]],"date-time":"2023-06-22T00:00:00Z","timestamp":1687392000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2023,12,30]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:sec>\n                  <jats:title>Background and Aims<\/jats:title>\n                  <jats:p>Nudix hydrolase 15 [NUDT15] genetic variants confer an increased risk of thiopurine-induced leukopenia [TIL]; however, their global prevalence in inflammatory bowel disease [IBD] patients is unknown. We aimed to evaluate the global prevalence of NUDT15 variants in IBD patients and incidence of TIL in these patients.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>Six databases were searched from inception until July 2022. Studies reporting the frequency of any NUDT15 variant and\/or frequency of leukopenia in adult IBD patients with these variants were included. A random effects model was performed to estimate the pooled prevalence of variants, incidence of early [\u22648 weeks] and late [&amp;gt;8 weeks] leukopenia, and relative risk of developing leukopenia.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>Twenty studies comprising 5232 patients were included. The pooled prevalence of the *1\/*3 c.415C\u2005&amp;gt;\u2005T C\/T diplotype was 13% (95% confidence interval [CI]: 10\u201318%), *3\/*3 c.415C\u2005&amp;gt;\u2005T T\/T diplotype was 2% [95% CI: 1\u20132%], *1\/*5 c.52G\u2005&amp;gt;\u2005A G\/A diplotype was 2% [95% CI: 1\u20133%], and *1\/*6 c.36_37insGGAGTC ins\/- diplotype was 7% [95% CI: 4\u201312%]. The pooled prevalence of *1\/*3 was high in Japanese [20%, 95% CI: 16\u201324%] and Chinese patients [18%, 95% CI: 12\u201327%]. The incidence of early leukopenia was 20% [95% CI: 16\u201326%] in *1\/*3 patients, 99% [95% CI: 7\u2013100%] in *3\/*3 patients, and 49% [95% CI: 29\u201369%] in *1\/*6 patients. The incidence of late leukopenia was 36% [95% CI: 26\u201349%] in *1\/*3 patients.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusions<\/jats:title>\n                  <jats:p>NUDT15 variants are common and strongly predict TIL in IBD patients. Pre-treatment NUDT15 genotyping should be considered particularly in Asian populations, to guide thiopurine dosing and prevent myelotoxicity.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1093\/ecco-jcc\/jjad107","type":"journal-article","created":{"date-parts":[[2023,6,22]],"date-time":"2023-06-22T20:49:29Z","timestamp":1687466969000},"page":"1920-1930","source":"Crossref","is-referenced-by-count":15,"title":["Prevalence of <i>NUDT15<\/i> Genetic Variants and Incidence of Thiopurine-induced Leukopenia in Inflammatory Bowel Disease: A Systematic Review and Meta-analysis"],"prefix":"10.1093","volume":"17","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7283-7246","authenticated-orcid":false,"given":"Natalie","family":"Yu","sequence":"first","affiliation":[{"name":"Department of Gastroenterology, St Vincent\u2019s Hospital Melbourne , Melbourne, VIC , Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8326-0761","authenticated-orcid":false,"given":"Danujan","family":"Sriranganathan","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology, Whipps Cross University Hospital, Barts Health NHS Trust , London , UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gareth J","family":"Walker","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology and Hepatology, Royal Brisbane and Women\u2019s Hospital Brisbane , Brisbane, QLD , Australia"},{"name":"Faculty of Medicine, University of Queensland , Brisbane, QLD , Australia"},{"name":"Gut Health Research Group, QIMR Berghofer Medical Research Institute , Brisbane, QLD , Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aleksejs","family":"Sazonovs","sequence":"additional","affiliation":[{"name":"Genomics of Inflammation and Immunity Group, Wellcome Sanger Institute , Hinxton , UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Helen","family":"Wilding","sequence":"additional","affiliation":[{"name":"Library Service, St Vincent\u2019s Hospital Melbourne , Melbourne, VIC , Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6215-8044","authenticated-orcid":false,"given":"Christopher","family":"Roberts","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology, Royal Devon and Exeter Hospital NHS Foundation Trust , Exeter , UK"},{"name":"Inflammatory Bowel Disease and Pharmacogenetics Research Group, University of Exeter , Exeter , UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicholas A","family":"Kennedy","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology, Royal Devon and Exeter Hospital NHS Foundation Trust , Exeter , UK"},{"name":"Inflammatory Bowel Disease and Pharmacogenetics Research Group, University of Exeter , Exeter , UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6058-5528","authenticated-orcid":false,"given":"Tariq","family":"Ahmad","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology, Royal Devon and Exeter Hospital NHS Foundation Trust , Exeter , UK"},{"name":"Inflammatory Bowel Disease and Pharmacogenetics Research Group, University of Exeter , Exeter , UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ray K","family":"Boyapati","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology, Monash Health , Melbourne, VIC , Australia"},{"name":"Faculty of Medicine, Nursing & Health Sciences, Monash University , Melbourne, VIC , Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6232-1948","authenticated-orcid":false,"given":"Nik 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