Functional characterization of 26 CYP2B6 allelic variants (CYP2B6.2-CYP2B6.28, except CYP2B6.22)

Takashi Watanabe, Kanako Sakuyama, Takamitsu Sasaki, Yuya Ishii, Masaaki Ishikawa, Noriyasu Hirasawa, Masahiro Hiratsuka

Research output: Contribution to journalArticle

35 Citations (Scopus)

Abstract

Cytochrome P450 2B6 (CYP2B6) is a potentially important enzyme for the metabolism of clinical drugs, and it exhibits genetic polymorphism. Thus far, 29 allelic variants of CYP2B6 (CYP2B6*1-CYP2B6*29) have been identified. This study aimed to investigate whether 26 of the variant alleles of CYP2B6 (CYP2B6*2-CYP2B6*21 and CYP2B6*23-CYP2B6*28) affect its kinetics in the metabolism of 7-ethoxy-4-trifluoromethylcoumarin (7-EFC) and selegiline. Wild-type CYP2B6.1 and the allelic variants were heterologously expressed in COS-7 cells. In-vitro kinetic analysis revealed that when compared with the wild-type protein CYP2B6.1, CYP2B6.10 and CYP2B6.14 exhibited significantly lower Vmax/Km values for selegiline N-demethylation. The kinetic parameters of CYP2B6.8, CYP2B6.11, CYP2B6.12, CYP2B6.13, CYP2B6.15, CYP2B6.18, CYP2B6.21, CYP2B6.24, and CYP2B6.28 could not be determined because these enzymes were inactive in the deethylation of 7-EFC and the N-demethylation/N-depropagylation of selegiline. These findings provide useful information for further genotype-phenotype studies on interindividual differences in the metabolism of CYP2B6 substrate drugs.

Original languageEnglish
Pages (from-to)459-462
Number of pages4
JournalPharmacogenetics and Genomics
Volume20
Issue number7
DOIs
Publication statusPublished - 2010 Jul 1

Keywords

  • 7-ethoxy-4-trifluoromethylcoumarin
  • CYP2B6
  • alleles
  • cytochrome P450
  • genetic polymorphism
  • selegiline

ASJC Scopus subject areas

  • Molecular Medicine
  • Molecular Biology
  • Genetics
  • Genetics(clinical)

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