Title :

A Robust and Fast/Multiplex Pharmacogenetics Assay to Simultaneously Analyze 17 Clinically Relevant Genetic Polymorphisms in CYP3A4, CYP3A5, CYP1A2, CYP2C9, CYP2C19, CYP2D6, ABCB1, and VKORC1 Genes

Author(s) :

Tron, Camille [Auteur]
Bouvet, Régis [Auteur]
Verdier, Marie-Clémence [Auteur]
Lamoureux, Fabien [Auteur]
Hennart, Benjamin [Auteur]
Toxicologie et Génopathies [CHRU Lille]
Dubourg, Christèle [Auteur]
Bellissant, Eric [Auteur]
Galibert, Marie-Dominique [Auteur]

Journal title :

Pharmaceuticals

Abbreviated title :

Pharmaceuticals (Basel)

Volume number :

15

Pages :

637

Publisher :

MDPI

Publication date :

2022-05-22

ISSN :

1424-8247

English keyword(s) :

pharmacogenetics
panel
multiplex
CYP450
personalized medicine

HAL domain(s) :

Sciences du Vivant [q-bio]
Sciences du Vivant [q-bio]/Sciences pharmaceutiques
Sciences du Vivant [q-bio]/Génétique/Génétique humaine

English abstract : [en]

In the field of pharmacogenetics, the trend is to analyze a panel of several actionable genetic polymorphisms. It may require the use of high-throughput sequencing which demands expensive reagents/instruments and specific ...
Show more >In the field of pharmacogenetics, the trend is to analyze a panel of several actionable genetic polymorphisms. It may require the use of high-throughput sequencing which demands expensive reagents/instruments and specific skills to interpret results. As an alternative, the aim of this work was to validate an easy, fast, and inexpensive multiplex pharmacogenetics assay to simultaneously genotype a panel of 17 clinically actionable variants involved in drug pharmacokinetics/pharmacodynamics. We designed primers to perform a multiplex PCR assay using a single mix. Primers were labeled by two fluorescent dye markers to discriminate alleles, while the size of the PCR fragments analyzed by electrophoresis allowed identifying amplicon. Polymorphisms of interest were CYP3A4*22, CYP3A5*3, CYP1A2*1F, CYP2C9*2-*3, CYP2C19*2-*3-*17, VKORC1-1639G > A, ABCB1 rs1045642-rs1128503-rs2229109-rs2032582, and CYP2D6*3-*4-*6-*9. The assay was repeatable and a minimum quantity of 10 ng of DNA/ sample was needed to obtain accurate results. The method was applied to a validation cohort of 121 samples and genotyping results were consistent with those obtained with reference methods. The assay was fast and cost-effective with results being available within one working-day. This robust assay can easily be implemented in laboratories as an alternative to cumbersome simplex assays or expensive multiplex approaches. Together it should widespread access to pharmacogenetics in clinical routine practice.Show less >

Language :

Anglais

Peer reviewed article :

Oui

Audience :

Internationale

Popular science :

Non

Administrative institution(s) :

Université de Lille
CHU Lille
Institut Pasteur de Lille

Collections :

• Autres travaux scientifiques

Submission date :

2023-10-20T06:04:48Z
2024-02-28T15:35:16Z