Update on next generation sequencing of pharmacokinetics-related genes: Development of the PKseq panel, a platform for amplicon sequencing of drug-metabolizing enzyme and drug transporter genes

• Published in: Drug metabolism and pharmacokinetics 2021-04, Vol.37, p.100370, Article 100370
• Main Authors: Fukunaga, Koya, Momozawa, Yukihide, Mushiroda, Taisei
• Format: Article
• Language: English
• Subjects: Biomarkers; Next generation sequencing; Pharmacogene; Pharmacogenomics; PKseq; Variant; WES; WGS
• ISSN: 1347-4367; 1880-0920
• DOI: 10.1016/j.dmpk.2020.11.005

Genetic variation in pharmacokinetics (PK)-related genes encoding drug metabolizing enzymes or drug transporters is one of the most practical pharmacogenetic biomarkers for the prediction or explanation of an individual’s response to drugs. Many pharmacogenomic variations are identified using targeted, whole-exome, and whole-genome sequencing, and the number of known novel variations and alleles in PK-related genes is increasing. The high homology of sequences among PK-related genes is suspected to lead to potential read misalignment and genotyping errors when short-read sequencing was performed. Therefore, highly efficient and accurate next generation sequencing (NGS) platforms for the sequencing of PK-related genes are needed. We have developed PKseq, a targeted sequencing panel based on multiplex PCR, which targets the coding regions of 37 drug transporters, 30 cytochrome P450 isoforms, 10 UDP-glucuronosyltransferases, 5 flavin-containing monooxygenases, 4 glutathione S-transferases, 4 sulfotransferases, and 10 other genes. In this review, we describe the current NGS platforms for the sequencing of PK-related genes. The NGS platforms, including the PKseq panel, will be useful not only for the identification of all the variants of PK-related genes associated with adverse drug reactions and drug efficacy, but also for clinical sequencing to achieve pharmacogenomics-based stratified medicine. [Display omitted]