Development and application of a rapid and sensitive genotyping method for pharmacogene variants using the single-stranded tag hybridization chromatographic printed-array strip (STH-PAS)

Masaki Kumondai, Akio Ito, Eiji Hishinuma, Aoi Kikuchi, Takahiro Saito, Masamitsu Takahashi, Chiharu Tsukada, Sakae Saito, Jun Yasuda, Masao Nagasaki, Naoko Minegishi, Masayuki Yamamoto, Akira Kaneko, Isao Teramoto, Masatsugu Kimura, Noriyasu Hirasawa, Masahiro Hiratsuka

Research output: Contribution to journalArticle

Abstract

Genetic polymorphisms contribute to inter-individual variability in the metabolism of multiple clinical drugs, including warfarin, thiopurines, primaquine, and aminoglycosides. A rapid and sensitive clinical assessment of various genome biomarkers is, therefore, required to predict the individual responsiveness of each patient to these drugs. In this study, we developed a novel genotyping method for the detection of nine pharmacogene variants that are important in the prediction of drug efficiency and toxicity. This genotyping method uses competitive allele-specific PCR and a single-stranded tag hybridization chromatographic printed-array strip (STH-PAS) that can unambiguously determine the presence or absence of the gene variant by displaying visible blue lines on the chromatographic printed-array strip. Notably, the results of our STH-PAS method were in 100% agreement with those obtained using standard Sanger sequencing and KASP assay genotyping methods for CYP4F2 gene deletion. Moreover, the results were obtained within 90 min, including the PCR amplification and signal detection processes. The sensitive and rapid nature of this novel method make it ideal for clinical genetic testing to predict drug efficacy and toxicity, and in doing so will aid in the development of individualized medicine and better patient care.

Original languageEnglish
Pages (from-to)258-263
Number of pages6
JournalDrug metabolism and pharmacokinetics
Volume33
Issue number6
DOIs
Publication statusPublished - 2018 Dec

Keywords

  • G6PD
  • Genetic polymorphisms
  • Mitochondrial DNA
  • Thiopurine
  • Warfarin

ASJC Scopus subject areas

  • Pharmacology
  • Pharmaceutical Science
  • Pharmacology (medical)

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