Evidence map›Paper›PMID 38788739›Full record

ArticleInflammatory bowel diseases2024

Landscape of TPMT and NUDT15 Pharmacogenetic Variation in a Cohort of Canadian Pediatric Inflammatory Bowel Disease Patients.

April M Kennedy, Anne M Griffiths, Aleixo M Muise, Thomas D Walters, Amanda Ricciuto, Hien Q Huynh, Eytan Wine, Kevan Jacobson, Sally Lawrence, Nicholas Carman and 17 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Inflammatory bowel diseases, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
6citing papers in PubMed, 1 pooled it
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

6 citing papers in PubMed, 1 synthesis or guideline pooled it.

  1. Pooled it
  2. Review
  3. Genomics in Health and Biomedicine.Advances in experimental medicine and biology · 2026
    Review
  4. Article
  5. Medical sciences (Basel, Switzerland) · 2025
    Review
  6. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

27 authors.

April M KennedyDivision of Clinical Pharmacology and Toxicology, The Hospital for Sick Children, Toronto, Ontario, Canada.
Anne M GriffithsSickKids IBD Centre, Division of Gastroenterology, Hepatology & Nutrition, The Hospital for Sick Children, Toronto, Ontario, Canada.ORCID 0000-0001-8623-4665
Aleixo M MuiseSickKids IBD Centre, Division of Gastroenterology, Hepatology & Nutrition, The Hospital for Sick Children, Toronto, Ontario, Canada.
Thomas D WaltersSickKids IBD Centre, Division of Gastroenterology, Hepatology & Nutrition, The Hospital for Sick Children, Toronto, Ontario, Canada.ORCID 0000-0002-4184-4600
Amanda RicciutoSickKids IBD Centre, Division of Gastroenterology, Hepatology & Nutrition, The Hospital for Sick Children, Toronto, Ontario, Canada.
Hien Q HuynhEdmonton Pediatric IBD Clinic, Department of Pediatrics, University of Alberta, Edmonton, Alberta, Canada.ORCID 0000-0002-7295-7595
Eytan WineEdmonton Pediatric IBD Clinic, Department of Pediatrics, University of Alberta, Edmonton, Alberta, Canada.ORCID 0000-0002-3458-4142
Kevan JacobsonDivision of Pediatric Gastroenterology, Hepatology and Nutrition, Department of Pediatrics, BC Children's Hospital, University of British Columbia, Vancouver, BC, Canada.ORCID 0000-0001-7269-8557
Sally LawrenceDivision of Pediatric Gastroenterology, Hepatology and Nutrition, Department of Pediatrics, BC Children's Hospital, University of British Columbia, Vancouver, BC, Canada.
Nicholas CarmanSickKids IBD Centre, Division of Gastroenterology, Hepatology & Nutrition, The Hospital for Sick Children, Toronto, Ontario, Canada.
David R MackCHEO IBD Centre, Division of Gastroenterology, Hepatology and Nutrition, Department of Pediatrics, Children's Hospital of Eastern Ontario, CHEO Research Institute and Department of Pediatrics, University of Ottawa, Ottawa, Canada.
Jennifer C deBruynDepartment of Pediatrics, Alberta Children's Hospital Research Institute (ACHRI), University of Calgary, Calgary, Alberta, Canada.
Anthony R OtleyDivision of Pediatric Gastroenterology & Nutrition, Department of Pediatrics, IWK Health Centre, Dalhousie University, Halifax, Nova Scotia, Canada.
Colette DeslandresDivision of Pediatric Gastroenterology, Hepatology and Nutrition, CHU Sainte-Justine, Montréal, Quebec, Canada.
Wael El-MatarySection of Pediatric Gastroenterology, Winnipeg Children's Hospital, University of Manitoba, Winnipeg, MB, Canada.
Mary ZachosDivision of Gastroenterology, Hepatology and Nutrition, Department of Pediatrics, McMaster University, Hamilton, Ontario, Canada.
Eric I BenchimolSickKids IBD Centre, Division of Gastroenterology, Hepatology & Nutrition, The Hospital for Sick Children, Toronto, Ontario, Canada.
Jeffrey CritchFaculty of Medicine, Memorial University, St John's, Newfoundland & Labrador, Canada.
Rilla SchneiderDivision of Gastroenterology and Nutrition, Department of Pediatrics, Montreal Children's Hospital, Montreal, Quebec, Canada.
Eileen CrowleyDepartment of Pediatrics, Division of Pediatric Gastroenterology & Hepatology, Children's Hospital Western Ontario, Western University, London, Ontario, Canada.ORCID 0000-0002-9545-4384
Michael LiThe Centre for Computational Medicine, The Hospital for Sick Children, Toronto, Ontario, Canada.
Neil WarnerCell Biology Program, SickKids Research Institute, The Hospital for Sick Children, Toronto, Ontario, Canada.
Dermot P B McGovernF. Widjaja Foundation Inflammatory Bowel and Immunobiology Research Institute, Cedars-Sinai Medical Center, Los Angeles, California, USA.
Dalin LiF. Widjaja Foundation Inflammatory Bowel and Immunobiology Research Institute, Cedars-Sinai Medical Center, Los Angeles, California, USA.
Talin HarituniansF. Widjaja Foundation Inflammatory Bowel and Immunobiology Research Institute, Cedars-Sinai Medical Center, Los Angeles, California, USA.ORCID 0000-0002-9005-7750
Sarah RudinDivision of Clinical Pharmacology and Toxicology, The Hospital for Sick Children, Toronto, Ontario, Canada.
Iris CohnDivision of Clinical Pharmacology and Toxicology, The Hospital for Sick Children, Toronto, Ontario, Canada.ORCID 0000-0002-3453-9421

Funding

Utilizing the Phenomics of IBD to Enhance Gene DiscoveryU01DK062413 · NIDDK · CEDARS-SINAI MEDICAL CENTER · PI Dermot Patrick McGovern · 2002 to 2026
$12.2M
Canadian Institute of Health Research (CIHR) 297862Children's Intestinal and Liver Disease (CH.I.L.D.)Hemsley Charitable TrustNIDDK NIH HHS U01 DK062413The Hospital for Sick Children Inflammatory Bowel Disease Center
6 · The paper itself

Abstract

backgroundPatients 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.

methodsPharmacogenetic 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.

resultsCollectively, 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).

conclusionsThese findings demonstrate the considerable interpopulation variability in PGx variation underlying thiopurine metabolism, which should be factored into testing diverse patient populations.

Indexed as

MethyltransferasesPyrophosphatasesAdolescentAzathioprineCanadaChildChild, PreschoolCohort StudiesColitis, UlcerativeCrohn DiseaseFemaleGenotypeHumansImmunosuppressive AgentsInflammatory Bowel DiseasesMaleAzathioprineImmunosuppressive AgentsMercaptopurineMethyltransferasesNudix HydrolasesNUDT15 protein, humanPyrophosphatasesthiopurine methyltransferaseTPMT protein, humangenetic ancestryNUDT15pharmacogeneticsthiopurinesTPMT

Identifiers

PMID38788739
PMCPMC11630297

What OpenQuestion holds

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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.