A Genomewide Association Study of Oxypurinol Concentrations in Patients Treated with Allopurinol

How to cite: Meloche, M.; Provost, S.; Leclair, G.; Oussaïd, E.; St-Jean, I.; Jutras, M.; Gaulin, M.-J.; Lemieux Perreault, L.-P.; Valois, D.; Mongrain, I.; Busseuil, D.; Rouleau, J.-L.; Tardif, J.-C.; Dubé, M.-P.; de Denus, S. A Genomewide Association Study of Oxypurinol Concentrations in Patients Treated with Allopurinol. Preprints 2024, 2024051092. https://doi.org/10.20944/preprints202405.1092.v1 Meloche, M.; Provost, S.; Leclair, G.; Oussaïd, E.; St-Jean, I.; Jutras, M.; Gaulin, M.-J.; Lemieux Perreault, L.-P.; Valois, D.; Mongrain, I.; Busseuil, D.; Rouleau, J.-L.; Tardif, J.-C.; Dubé, M.-P.; de Denus, S. A Genomewide Association Study of Oxypurinol Concentrations in Patients Treated with Allopurinol. Preprints 2024, 2024051092. https://doi.org/10.20944/preprints202405.1092.v1

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MDPI and ACS Style

Meloche, M.; Provost, S.; Leclair, G.; Oussaïd, E.; St-Jean, I.; Jutras, M.; Gaulin, M.-J.; Lemieux Perreault, L.-P.; Valois, D.; Mongrain, I.; Busseuil, D.; Rouleau, J.-L.; Tardif, J.-C.; Dubé, M.-P.; de Denus, S. A Genomewide Association Study of Oxypurinol Concentrations in Patients Treated with Allopurinol. Preprints 2024, 2024051092. https://doi.org/10.20944/preprints202405.1092.v1

APA Style

Meloche, M., Provost, S., Leclair, G., Oussaïd, E., St-Jean, I., Jutras, M., Gaulin, M. J., Lemieux Perreault, L. P., Valois, D., Mongrain, I., Busseuil, D., Rouleau, J. L., Tardif, J. C., Dubé, M. P., & de Denus, S. (2024). A Genomewide Association Study of Oxypurinol Concentrations in Patients Treated with Allopurinol. Preprints. https://doi.org/10.20944/preprints202405.1092.v1

Chicago/Turabian Style

Meloche, M., Marie-Pierre Dubé and Simon de Denus. 2024 "A Genomewide Association Study of Oxypurinol Concentrations in Patients Treated with Allopurinol" Preprints. https://doi.org/10.20944/preprints202405.1092.v1

Abstract

Cohort studies have identified several genetic determinants that could predict the clinical response to allopurinol. However, they have not been commonly used for genome-wide investigations to identify genetic determinants on allopurinol metabolism and concentrations. We conducted a genome-wide association study of a prior cross-sectional investigation of patients from the Montreal Heart Institute Biobank undergoing allopurinol therapy. Four endpoints were investigated, namely plasma concentrations of oxypurinol, the active metabolite of allopurinol, allopurinol, and allopurinol-riboside, as well as allopurinol daily dosing. A total of 439 participants (mean age 69.4 years; 86.4% male) taking allopurinol (mean daily dose 194.5 mg) and who had quantifiable oxypurinol concentrations were included in the genome-wide analyses. Participants presented multiple comorbidities and received concomitant cardiovascular medications. No association achieved the predefined genome-wide threshold values for any of the endpoints (all p>5 × 10-8). Our results are consistent with prior finding regarding the difficulty in identifying genetic determinants of drug concentrations or pharmacokinetics of allopurinol and its metabolites, and allopurinol daily dosing. Given the size of this genome-wide study, collaborative investigations involving larger and diverse cohorts may be required to further identify pharmacogenomic determinants of allopurinol and measure their clinical relevance to personalize allopurinol therapy.

Keywords

GWAS; pharmacogenomics; allopurinol; drug metabolism; biobank

Subject

Medicine and Pharmacology, Pharmacology and Toxicology

Copyright: This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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