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

IF 1.9 4区医学 Q3 PHARMACOLOGY & PHARMACY Pharmacogenomics Pub Date : 2023-06-01 DOI:10.2217/pgs-2023-0067

Jean Laverdière, Maxime Meloche, Sylvie Provost, Grégoire Leclair, Essaïd Oussaïd, Martin Jutras, Louis-Philippe Lemieux Perreault, Diane Valois, Ian Mongrain, David Busseuil, Jean Lucien Rouleau, Jean-Claude Tardif, Marie-Pierre Dubé, Simon de Denus

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Abstract

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.

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美托洛尔和α- oh -美托洛尔浓度的药物基因组学标记:全基因组关联研究。

目的:很少进行全基因组关联研究(GWASs)来确定药物浓度的预测因子。因此，作者试图发现美托洛尔药代动力学中涉及的药物基因组学标记。患者和方法:作者对来自蒙特利尔心脏研究所生物库的993名服用美托洛尔的患者进行了横断面研究的GWAS。结果:分别有391个和444个snp达到美托洛尔和α- oh -美托洛尔浓度5 × 10-8的显著性阈值。它们都位于22号染色体上CYP2D6基因附近，该基因编码美托洛尔的主要代谢酶CYP450 2D6。结论:该结果加强了先前CYP2D6位点对美托洛尔浓度的重要性的发现，并证实了大型生物库可以在GWAS显著水平上用于鉴定药物药代动力学的遗传决定因素。

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来源期刊

Pharmacogenomics 医学-药学

CiteScore

3.40

自引率

9.50%

发文量

审稿时长

4-8 weeks

期刊介绍： Pharmacogenomics (ISSN 1462-2416) is a peer-reviewed journal presenting reviews and reports by the researchers and decision-makers closely involved in this rapidly developing area. Key objectives are to provide the community with an essential resource for keeping abreast of the latest developments in all areas of this exciting field. Pharmacogenomics is the leading source of commentary and analysis, bringing you the highest quality expert analyses from corporate and academic opinion leaders in the field.