{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,8]],"date-time":"2026-10-08T16:13:02Z","timestamp":1791475982338,"version":"4.3.4"},"reference-count":45,"publisher":"Oxford University Press (OUP)","issue":"12","license":[{"start":{"date-parts":[[2024,5,24]],"date-time":"2024-05-24T00:00:00Z","timestamp":1716508800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100000024","name":"Canadian Institute of Health Research","doi-asserted-by":"crossref","award":["297862"],"award-info":[{"award-number":["297862"]}],"id":[{"id":"10.13039\/501100000024","id-type":"DOI","asserted-by":"crossref"}]},{"name":"Children\u2019s Intestinal and Liver Disease"},{"name":"The Hospital for Sick Children Inflammatory Bowel Disease Center"},{"name":"Hemsley Charitable Trust"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2024,12,5]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Patients with inflammatory bowel disease (IBD) exhibit considerable interindividual variability in medication response, highlighting the need for precision medicine approaches to optimize and tailor treatment. Pharmacogenetics (PGx) offers the ability to individualize dosing by examining genetic factors underlying the metabolism of medications such as thiopurines. Pharmacogenetic testing can identify individuals who may be at risk for thiopurine dose-dependent adverse reactions including myelosuppression. We aimed to evaluate PGx variation in genes supported by clinical guidelines that inform dosing of thiopurines and characterize differences in the distribution of actionable PGx variation among diverse ancestral groups.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Pharmacogenetic variation in TPMT and NUDT15 was captured by genome-wide genotyping of 1083 pediatric IBD patients from a diverse Canadian cohort. Genetic ancestry was inferred using principal component analysis. The proportion of PGx variation and associated metabolizer status phenotypes was compared across 5 genetic ancestral groups within the cohort (Admixed American, African, East Asian, European, and South Asian) and to prior global estimates from corresponding populations.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Collectively, 11% of the cohort was categorized as intermediate or poor metabolizers of thiopurines, which would warrant a significant dose reduction or selection of alternate therapy. Clinically actionable variation in TPMT was more prevalent in participants of European and Admixed American\/Latino ancestry (8.7% and 7.5%, respectively), whereas variation in NUDT15 was more prevalent in participants of East Asian and Admixed American\/Latino ancestry (16% and 15% respectively).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>These findings demonstrate the considerable interpopulation variability in PGx variation underlying thiopurine metabolism, which should be factored into testing diverse patient populations.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1093\/ibd\/izae109","type":"journal-article","created":{"date-parts":[[2024,5,16]],"date-time":"2024-05-16T16:31:53Z","timestamp":1715877113000},"page":"2418-2427","source":"Crossref","is-referenced-by-count":13,"title":["Landscape of\n                    <i>TPMT<\/i>\n                    and\n                    <i>NUDT15<\/i>\n                    Pharmacogenetic Variation in a Cohort of Canadian Pediatric Inflammatory Bowel Disease Patients"],"prefix":"10.1093","volume":"30","author":[{"given":"April M","family":"Kennedy","sequence":"first","affiliation":[{"name":"Division of Clinical Pharmacology and Toxicology, The Hospital for Sick Children , Toronto, Ontario ,","place":["Canada"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8623-4665","authenticated-orcid":false,"given":"Anne M","family":"Griffiths","sequence":"additional","affiliation":[{"name":"SickKids IBD Centre, Division of Gastroenterology, Hepatology & Nutrition, The Hospital for Sick Children , Toronto, Ontario ,","place":["Canada"]},{"name":"Child Health Evaluative Sciences, SickKids Research Institute, The Hospital for Sick Children , Toronto, Ontario ,","place":["Canada"]},{"name":"Department of Paediatrics, University of Toronto , Toronto, Ontario ,","place":["Canada"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aleixo M","family":"Muise","sequence":"additional","affiliation":[{"name":"SickKids IBD Centre, Division of Gastroenterology, Hepatology & Nutrition, The Hospital for Sick Children , Toronto, Ontario ,","place":["Canada"]},{"name":"Department of Paediatrics, University of Toronto , Toronto, Ontario ,","place":["Canada"]},{"name":"Department of Biochemistry, University of Toronto , Toronto, Ontario ,","place":["Canada"]},{"name":"Cell Biology Program, SickKids Research Institute, The Hospital for Sick Children , Toronto, Ontario ,","place":["Canada"]},{"name":"Institute of Medical Science, University of Toronto , Toronto, Ontario ,","place":["Canada"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4184-4600","authenticated-orcid":false,"given":"Thomas D","family":"Walters","sequence":"additional","affiliation":[{"name":"SickKids IBD Centre, Division of 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Department of Pediatrics, University of Alberta , Edmonton, Alberta ,","place":["Canada"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3458-4142","authenticated-orcid":false,"given":"Eytan","family":"Wine","sequence":"additional","affiliation":[{"name":"Edmonton Pediatric IBD Clinic, Department of Pediatrics, University of Alberta , Edmonton, Alberta ,","place":["Canada"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7269-8557","authenticated-orcid":false,"given":"Kevan","family":"Jacobson","sequence":"additional","affiliation":[{"name":"Division of Pediatric Gastroenterology, Hepatology and Nutrition, Department of Pediatrics, BC Children\u2019s Hospital, University of British Columbia , Vancouver, BC ,","place":["Canada"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sally","family":"Lawrence","sequence":"additional","affiliation":[{"name":"Division of Pediatric Gastroenterology, Hepatology and Nutrition, Department of Pediatrics, BC Children\u2019s Hospital, University of British Columbia , Vancouver, BC ,","place":["Canada"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicholas","family":"Carman","sequence":"additional","affiliation":[{"name":"SickKids IBD Centre, Division of Gastroenterology, Hepatology & Nutrition, The Hospital for Sick Children , Toronto, Ontario ,","place":["Canada"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David R","family":"Mack","sequence":"additional","affiliation":[{"name":"CHEO IBD Centre, Division of Gastroenterology, Hepatology and Nutrition, Department of Pediatrics, Children\u2019s Hospital of Eastern Ontario, CHEO Research Institute and Department of Pediatrics, University of Ottawa , Ottawa ,","place":["Canada"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jennifer C","family":"deBruyn","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Alberta Children\u2019s Hospital Research Institute (ACHRI), University of Calgary , Calgary, Alberta ,","place":["Canada"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anthony R","family":"Otley","sequence":"additional","affiliation":[{"name":"Division of Pediatric Gastroenterology & Nutrition, Department of Pediatrics, IWK Health Centre, Dalhousie University , Halifax, Nova Scotia ,","place":["Canada"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Colette","family":"Deslandres","sequence":"additional","affiliation":[{"name":"Division of Pediatric Gastroenterology, Hepatology and Nutrition, CHU Sainte-Justine , Montr\u00e9al, Quebec ,","place":["Canada"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wael","family":"El-Matary","sequence":"additional","affiliation":[{"name":"Section of Pediatric Gastroenterology, Winnipeg Children\u2019s Hospital, University of Manitoba , Winnipeg, MB 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,","place":["Canada"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael","family":"Li","sequence":"additional","affiliation":[{"name":"The Centre for Computational Medicine, The Hospital for Sick Children , Toronto, Ontario ,","place":["Canada"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Neil","family":"Warner","sequence":"additional","affiliation":[{"name":"Cell Biology Program, SickKids Research Institute, The Hospital for Sick Children , Toronto, Ontario ,","place":["Canada"]},{"name":"SickKids IBD Centre, Division of Gastroenterology, Hepatology & Nutrition, The Hospital for Sick Children , Toronto, Ontario ,","place":["Canada"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dermot P B","family":"McGovern","sequence":"additional","affiliation":[{"name":"F. 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