Clinical Implications of Combinatorial Pharmacogenomic Tests Based on Cytochrome P450 Variant Selection

Authors

Michael R. Sayer, Chapman University
Ashley Duche, Chapman UniversityFollow
Trang Jenny Tran Nguyen, Chapman University
Michelle Le, Chapman University
Kunj Patel, Chapman University
Jacqueline Vu, Chapman University
Danny Pham, Chapman University
Brianne Vernick, Chapman University
Richard Beuttler, Chapman UniversityFollow
Don Roosan, Western University of Health Sciences
Moom R. Roosan, Chapman UniversityFollow

Document Type

Article

Publication Date

9-28-2021

Abstract

Despite the potential to improve patient outcomes, the application of pharmacogenomics (PGx) is yet to be routine. A growing number of PGx implementers are leaning toward using combinatorial PGx (CPGx) tests (i.e., multigene tests) that are reusable over patients’ lifetimes. However, selecting a single best available CPGx test is challenging owing to many patient- and population-specific factors, including variant frequency differences across ethnic groups. The primary objective of this study was to evaluate the detection rate of currently available CPGx tests based on the cytochrome P450 (CYP) gene variants they target. The detection rate was defined as the percentage of a given population with an “altered metabolizer” genotype predicted phenotype, where a CPGx test targeted both gene variants a prospective diplotypes. A potential genotype predicted phenotype was considered an altered metabolizer when it resulted in medication therapy modification based on Clinical Pharmacogenetics Implementation Consortium (CPIC) guidelines. Targeted variant CPGx tests found in the Genetic Testing Registry (GTR), gene selection information, and diplotype frequency data from the Pharmacogenomics Knowledge Base (PharmGKB) were used to determine the detection rate of each CPGx test. Our results indicated that the detection rate of CPGx tests covering CYP2C19, CYP2C9, CYP2D6, and CYP2B6 show significant variation across ethnic groups. Specifically, the Sub-Saharan Africans have 63.9% and 77.9% average detection rates for CYP2B6 and CYP2C19 assays analyzed, respectively. In addition, East Asians (EAs) have an average detection rate of 55.1% for CYP2C9 assays. Therefore, the patient’s ethnic background should be carefully considered in selecting CPGx tests.

Comments

This article was originally published in Frontiers in Genetics, volume 12, in 2021. https://doi.org/10.3389/fgene.2021.719671

Recommended Citation

Sayer M, Duche A, Nguyen TJT, Le M, Patel K, Vu J, Pham D, Vernick B, Beuttler R, Roosan D and Roosan MR (2021) Clinical Implications of Combinatorial Pharmacogenomic Tests Based on Cytochrome P450 Variant Selection. Front. Genet. 12:719671. https://doi.org/10.3389/fgene.2021.719671

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The authors

Creative Commons License

This work is licensed under a Creative Commons Attribution 4.0 License.