A Genome-Wide Association Study of Oxypurinol Concentrations in Patients Treated with Allopurinol.

Autor:	Meloche M; Faculty of Pharmacy, Université de Montréal, Montreal, QC H3T 1J4, Canada.; Montreal Heart Institute, Montreal, QC H1T 1C8, Canada.; Université de Montréal Beaulieu-Saucier Pharmacogenomics Centre, Montreal, QC H1T 1C8, Canada., Pilon MO; Faculty of Pharmacy, Université de Montréal, Montreal, QC H3T 1J4, Canada.; Montreal Heart Institute, Montreal, QC H1T 1C8, Canada.; Université de Montréal Beaulieu-Saucier Pharmacogenomics Centre, Montreal, QC H1T 1C8, Canada., Provost S; Montreal Heart Institute, Montreal, QC H1T 1C8, Canada.; Université de Montréal Beaulieu-Saucier Pharmacogenomics Centre, Montreal, QC H1T 1C8, Canada., Leclair G; Faculty of Pharmacy, Université de Montréal, Montreal, QC H3T 1J4, Canada., Oussaïd E; Montreal Heart Institute, Montreal, QC H1T 1C8, Canada.; Université de Montréal Beaulieu-Saucier Pharmacogenomics Centre, Montreal, QC H1T 1C8, Canada., St-Jean I; Faculty of Pharmacy, Université de Montréal, Montreal, QC H3T 1J4, Canada., Jutras M; Faculty of Pharmacy, Université de Montréal, Montreal, QC H3T 1J4, Canada., Gaulin MJ; Montreal Heart Institute, Montreal, QC H1T 1C8, Canada.; Université de Montréal Beaulieu-Saucier Pharmacogenomics Centre, Montreal, QC H1T 1C8, Canada., Lemieux Perreault LP; Montreal Heart Institute, Montreal, QC H1T 1C8, Canada.; Université de Montréal Beaulieu-Saucier Pharmacogenomics Centre, Montreal, QC H1T 1C8, Canada., Valois D; Montreal Heart Institute, Montreal, QC H1T 1C8, Canada.; Université de Montréal Beaulieu-Saucier Pharmacogenomics Centre, Montreal, QC H1T 1C8, Canada., Mongrain I; Montreal Heart Institute, Montreal, QC H1T 1C8, Canada.; Université de Montréal Beaulieu-Saucier Pharmacogenomics Centre, Montreal, QC H1T 1C8, Canada., Busseuil D; Montreal Heart Institute, Montreal, QC H1T 1C8, Canada.; Université de Montréal Beaulieu-Saucier Pharmacogenomics Centre, Montreal, QC H1T 1C8, Canada., Rouleau JL; Montreal Heart Institute, Montreal, QC H1T 1C8, Canada.; Faculty of Medicine, Université de Montréal, Montreal, QC H3T 1J4, Canada., Tardif JC; Montreal Heart Institute, Montreal, QC H1T 1C8, Canada.; Université de Montréal Beaulieu-Saucier Pharmacogenomics Centre, Montreal, QC H1T 1C8, Canada.; Faculty of Medicine, Université de Montréal, Montreal, QC H3T 1J4, Canada., Dubé MP; Montreal Heart Institute, Montreal, QC H1T 1C8, Canada.; Université de Montréal Beaulieu-Saucier Pharmacogenomics Centre, Montreal, QC H1T 1C8, Canada.; Faculty of Medicine, Université de Montréal, Montreal, QC H3T 1J4, Canada., de Denus S; Faculty of Pharmacy, Université de Montréal, Montreal, QC H3T 1J4, Canada.; Montreal Heart Institute, Montreal, QC H1T 1C8, Canada.; Université de Montréal Beaulieu-Saucier Pharmacogenomics Centre, Montreal, QC H1T 1C8, Canada.
Jazyk:	angličtina
Zdroj:	Journal of personalized medicine [J Pers Med] 2024 Jun 18; Vol. 14 (6). Date of Electronic Publication: 2024 Jun 18.
DOI:	10.3390/jpm14060649
Abstrakt:	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 with 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 findings regarding the difficulty in identifying genetic determinants of drug concentrations or pharmacokinetics of allopurinol and its metabolites, as well as 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.
Databáze:	MEDLINE
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