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Short Communication

Pharmacogenomic markers of metoprolol and α-OH-metoprolol concentrations: a genome-wide association study

    Jean Laverdière

    Faculty of Pharmacy, Université de Montréal, H3T 1J4, Montreal, Quebec, Canada

    Montreal Heart Institute, H1T 1C8, Montreal, Quebec, Canada

    Université de Montreal Beaulieu-Saucier Pharmacogenomics Centre, H1T 1C8, Montreal, Quebec, Canada

    ,
    Maxime Meloche

    Faculty of Pharmacy, Université de Montréal, H3T 1J4, Montreal, Quebec, Canada

    Montreal Heart Institute, H1T 1C8, Montreal, Quebec, Canada

    Université de Montreal Beaulieu-Saucier Pharmacogenomics Centre, H1T 1C8, Montreal, Quebec, Canada

    ,
    Sylvie Provost

    Montreal Heart Institute, H1T 1C8, Montreal, Quebec, Canada

    Université de Montreal Beaulieu-Saucier Pharmacogenomics Centre, H1T 1C8, Montreal, Quebec, Canada

    ,
    Grégoire Leclair

    Faculty of Pharmacy, Université de Montréal, H3T 1J4, Montreal, Quebec, Canada

    ,
    Essaïd Oussaïd

    Montreal Heart Institute, H1T 1C8, Montreal, Quebec, Canada

    Université de Montreal Beaulieu-Saucier Pharmacogenomics Centre, H1T 1C8, Montreal, Quebec, Canada

    ,
    Martin Jutras

    Faculty of Pharmacy, Université de Montréal, H3T 1J4, Montreal, Quebec, Canada

    ,
    Louis-Philippe Lemieux Perreault

    Montreal Heart Institute, H1T 1C8, Montreal, Quebec, Canada

    Université de Montreal Beaulieu-Saucier Pharmacogenomics Centre, H1T 1C8, Montreal, Quebec, Canada

    ,
    Diane Valois

    Montreal Heart Institute, H1T 1C8, Montreal, Quebec, Canada

    Université de Montreal Beaulieu-Saucier Pharmacogenomics Centre, H1T 1C8, Montreal, Quebec, Canada

    ,
    Ian Mongrain

    Montreal Heart Institute, H1T 1C8, Montreal, Quebec, Canada

    Université de Montreal Beaulieu-Saucier Pharmacogenomics Centre, H1T 1C8, Montreal, Quebec, Canada

    ,
    David Busseuil

    Montreal Heart Institute, H1T 1C8, Montreal, Quebec, Canada

    Université de Montreal Beaulieu-Saucier Pharmacogenomics Centre, H1T 1C8, Montreal, Quebec, Canada

    ,
    Jean Lucien Rouleau

    Montreal Heart Institute, H1T 1C8, Montreal, Quebec, Canada

    Faculty of Medicine, Université de Montréal, H3T 1J4, Montreal, Quebec, Canada

    ,
    Jean-Claude Tardif

    Montreal Heart Institute, H1T 1C8, Montreal, Quebec, Canada

    Université de Montreal Beaulieu-Saucier Pharmacogenomics Centre, H1T 1C8, Montreal, Quebec, Canada

    Faculty of Medicine, Université de Montréal, H3T 1J4, Montreal, Quebec, Canada

    ,
    Marie-Pierre Dubé

    Montreal Heart Institute, H1T 1C8, Montreal, Quebec, Canada

    Université de Montreal Beaulieu-Saucier Pharmacogenomics Centre, H1T 1C8, Montreal, Quebec, Canada

    Faculty of Medicine, Université de Montréal, H3T 1J4, Montreal, Quebec, Canada

    &
    Simon de Denus

    *Author for correspondence: Tel.: +1 514 376 3330;

    E-mail Address: simon.dedenus@icm-mhi.org

    Faculty of Pharmacy, Université de Montréal, H3T 1J4, Montreal, Quebec, Canada

    Montreal Heart Institute, H1T 1C8, Montreal, Quebec, Canada

    Université de Montreal Beaulieu-Saucier Pharmacogenomics Centre, H1T 1C8, Montreal, Quebec, Canada

    Published Online:https://doi.org/10.2217/pgs-2023-0067

    Aim: Few genome-wide association studies (GWASs) have been conducted to identify predictors of drug concentrations. The authors therefore sought to discover the pharmacogenomic markers involved in metoprolol pharmacokinetics. Patients & methods: The authors performed a GWAS of a cross-sectional study of 993 patients from the Montreal Heart Institute Biobank taking metoprolol. Results: A total of 391 and 444 SNPs reached the significance threshold of 5 × 10-8 for metoprolol and α-OH-metoprolol concentrations, respectively. All were located on chromosome 22 at or near the CYP2D6 gene, encoding CYP450 2D6, metoprolol's main metabolizing enzyme. Conclusion: The results reinforce previous findings of the importance of the CYP2D6 locus for metoprolol concentrations and confirm that large biobanks can be used to identify genetic determinants of drug pharmacokinetics at a GWAS significance level.

    Tweetable abstract

    Using large biobanks with randomly collected patient samples, a genome-wide association study confirms CYP2D6 as the principal genomic determinant of metoprolol concentrations while identifying new potential markers.

    Papers of special note have been highlighted as: • of interest; •• of considerable interest

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