Search

Pharmacogenetics promises to optimize treatment-related outcomes by informing optimal drug selection and dosing based on an individual's genotype in conjunction with other important clinical factors. Despite significant evidence of genetic associations with drug response, pharmacogenetic testing has not been widely implemented into clinical practice. Among the barriers to broad implementation are limited guidance for how to successfully integrate testing into clinical workflows and limited data on outcomes with pharmacogenetic implementation in clinical practice. The Pharmacogenomics Global Research Network Implementation Working Group seeks to engage institutions globally that have implemented pharmacogenetic testing into clinical practice or are in the process or planning stages of implementing testing to collectively disseminate data on implementation strategies, metrics, and health-related outcomes with the use of genotype-guided drug therapy to ultimately help advance pharmacogenetic implementation. This paper describes the goals, structure, and initial projects of the group in addition to implementation priorities across sites and future collaborative opportunities., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Background/objectives: The polymorphic hepatic enzyme CYP2C19 catalyzes the metabolism of clinically important drugs such as clopidogrel, proton-pump inhibitors, and others and clinical pharmacogenetic testing for clopidogrel is increasingly common. The CYP2C19*10 single-nucleotide polymorphism (SNP) is located 1 bp upstream the CYP2C19*2 SNP. Despite the low frequency of the CYP2C19*10 allele, its impact on metabolism of CYP2C19 substrates and CYP2C19*2 genotyping makes it an important SNP to consider for pharmacogenetic testing of CYP2C19. However, the effect of the CYP2C19*10 allele on clopidogrel metabolism has not been explored to date., Methods: We measured the enzymatic activity of the CYP2C19.10 protein against clopidogrel. DNA samples from two clinical studies were genotyped for CYP2C19*2 and *10 by pyrosequencing genotyping method., Results: The catalytic activity of CYP2C19.10 in the biotransformation of clopidogrel and 2-oxo-clopidogrel was significantly decreased relative to the wild-type CYP2C19.1B. We also reported that the CYP2C19*10 SNP interferes with the CYP2C19*2 TaqMan genotyping assay, resulting in miscalling of CYP2C19*10/*2 as CYP2C19*2/*2., Conclusions: Our data provide evidence that CYP2C19.10 variant partially metabolizes clopidogrel and 2-oxo-clopidogrel, and the presence of CYP2C19*10 allele affects the CY2C19*2 TaqMan genotyping assay and results in misclassification of CYP2C19*10/*2 as CYP2C19*2/*2.