{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,27]],"date-time":"2026-05-27T13:56:55Z","timestamp":1779890215585,"version":"3.53.1"},"reference-count":17,"publisher":"Wiley","issue":"11","license":[{"start":{"date-parts":[[2022,6,8]],"date-time":"2022-06-08T00:00:00Z","timestamp":1654646400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Internal Medicine Journal"],"published-print":{"date-parts":[[2022,11]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Thiopurine\u2010related adverse events such as leukopenia, liver dysfunction and pancreatitis are associated with variants in the <jats:italic>NUDT15<\/jats:italic> gene. Loss\u2010of\u2010function (low or no enzyme activity) alleles are more common in Asian and Hispanic populations. The prevalence of these variants in the Australian inflammatory bowel disease (IBD) population has not yet been reported.<\/jats:p><\/jats:sec><jats:sec><jats:title>Aim<\/jats:title><jats:p>To evaluate the presence of <jats:italic>NUDT15<\/jats:italic> loss\u2010of\u2010function alleles *2,*3,*9 in the Australian IBD population.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>The <jats:italic>NUDT15<\/jats:italic> screening cohort included 423 IBD patients from Brisbane, Australia. Study patients were recruited by: (i) retrospective review of clinical charts for thiopurine\u2010related severe adverse events; (ii) pathology data (white blood cell (WBC) and neutrophil counts). <jats:italic>NUDT15<\/jats:italic> genotyping was performed using polymerase chain reaction (PCR)\u2010high\u2010resolution melt (HRM), TaqMan genotyping and Sanger sequencing.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p><jats:italic>NUDT15<\/jats:italic> mutation R139C (allele *3) was identified in 8 of 423 (1.9%) IBD patients. Seven of eight patients were R139C heterozygous (C\/T) and one patient was R139C homozygous (T\/T). One of the C\/T group and the T\/T patient developed thiopurine\u2010induced myelosuppression (TIM) within 60\u2009days of dosing. One patient in the C\/T group developed TIM after 60\u2009days of thiopurine dosing. The remaining five patients in the C\/T group did not show TIM; however, other thiopurine\u2010related events could not be ruled out and therefore careful monitoring over a long period is recommended.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>This is the first study to report the frequency of <jats:italic>NUDT15<\/jats:italic> haplotypes *2,*3,*9 in an Australian IBD population. The most common variant detected was the R139C mutation. PCR and Sanger sequencing are efficient and cost\u2010effective approaches for <jats:italic>NUDT15<\/jats:italic> genotyping.<\/jats:p><\/jats:sec>","DOI":"10.1111\/imj.15746","type":"journal-article","created":{"date-parts":[[2022,3,15]],"date-time":"2022-03-15T06:58:14Z","timestamp":1647327494000},"page":"1971-1977","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Nudix hydrolase 15 (<i>NUDT15<\/i>) loss\u2010of\u2010function variants in an Australian inflammatory bowel disease population"],"prefix":"10.1111","volume":"52","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0501-2847","authenticated-orcid":false,"given":"Sadia","family":"Afrin","sequence":"first","affiliation":[{"name":"Gut Health Research Group QIMR Berghofer Medical Research Institute  Brisbane Queensland Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lisa 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