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Genetic association analysis and frequency of NUDT15*3 with thiopurine-induced myelosuppression in patients with inflammatory bowel disease in a large Dutch cohort

The Pharmacogenomics Journal volume 24, Article number: 39 (2024) Cite this article

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Abstract

Thiopurine drugs are cornerstone treatment for patients with inflammatory bowel disease (IBD). The most common adverse drug reaction is thiopurine-induced myelosuppression (TIM), that may partly be explained by the genetic polymorphism NUDT15*3. The aim of this retrospective study was to determine the NUDT15*3 polymorphism frequency and its association with TIM in an IBD patient population in the Netherlands. DNA from patients previously genotyped for TPMT was genotyped for NUDT15*3. In IBD patients treated with thiopurines association tests with TIM were conducted. Out of 988 included patients, 13 (1.3%) were heterozygous for NUDT15*3. Of all patients, 606 had IBD and received thiopurine treatment. In these patients, 8/606 (1.3%) were heterozygous polymorphic for NUDT15*3 of which 50.0% developed TIM compared to 2.3% in the wild type patients (p < 0.001). The study results show a clinically relevant prevalence of NUDT15*3 in the Dutch patient population. Its strong association with TIM suggests pre-therapeutic genotyping potentially clinically utile.

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Data availability

The datasets generated during and/or analysed during the current study are available from the corresponding author on reasonable request.

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Funding

The study was sponsored by the Catharina Hospital.

Author information

Authors and Affiliations

  1. Department of Clinical Pharmacy, Catharina Hospital, Eindhoven, the Netherlands

    Maarten J. Deenen & Anouk J. van Noordenburg

  2. Department of Clinical Pharmacy & Toxicology, Leiden University Medical Centre, Leiden, the Netherlands

    Maarten J. Deenen

  3. Department of Clinical Chemistry, Catharina Hospital, Eindhoven, the Netherlands

    Joëlle Bouwens-Bijsterveld & Birgit A. L. M. Deiman

  4. Department of Gastroenterology and Hepatology, Elkerliek Hospital, Helmond, the Netherlands

    Maarten A. van Dijk

  5. Department of Pediatrics, Catharina Hospital, Eindhoven, the Netherlands

    Janneke M. Stapelbroek

  6. Department of Clinical Pharmacy, Máxima Medical Centre, Eindhoven, the Netherlands

    Luc J. J. Derijks

  7. Department of Clinical Pharmacy & Toxicology, Maastricht University Medical Centre, Maastricht, the Netherlands

    Luc J. J. Derijks

  8. Department of Gastroenterology and Hepatology, Catharina Hospital, Eindhoven, the Netherlands

    Lennard P. L. Gilissen

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Contributions

MJD: conceptualization, data curation, methodology, project administration, resources, supervision, writing—original draft. AJvN: data curation, methodology, formal analysis, investigation, visualization, writing—original draft. JBB: data curation, investigation, writing—review and editing. MAvD: data curation, resources, validation, writing—review and editing. JMS: resources, writing—review and editing. LJJD: conceptualization, methodology, writing—review and editing. LPLG: conceptualization, investigation, methodology, resources, validation, writing—review and editing. BALMD: conceptualization, data curation, funding acquisition, methodology, resources, writing—review and editing. All authors approved the final version of the manuscript, including the authorship list. MJD acts as the guarantor of the article and takes responsibility for the integrity of the work as a whole.

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Correspondence to Maarten J. Deenen.

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Deenen, M.J., van Noordenburg, A.J., Bouwens-Bijsterveld, J. et al. Genetic association analysis and frequency of NUDT15*3 with thiopurine-induced myelosuppression in patients with inflammatory bowel disease in a large Dutch cohort. Pharmacogenomics J 24, 39 (2024). https://doi.org/10.1038/s41397-024-00358-7

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