SHORT COMMUNICATIONFunctional characterization of 26 CYP2B6 allelic variants (CYP2B6.2–CYP2B6.28, except CYP2B6.22)Watanabe, Takashia; Sakuyama, Kanakoa; Sasaki, Takamitsua; Ishii, Yuyaa; Ishikawa, Masaakia; Hirasawa, Noriyasub; Hiratsuka, MasahirobAuthor Information aDepartment of Clinical Pharmacotherapeutics, Tohoku Pharmaceutical University bLaboratory of Pharmacotherapy of Life-Style Related Diseases, Graduate School of Pharmaceutical Sciences, Tohoku University, Sendai, Japan Correspondence to Dr Masahiro Hiratsuka, PhD, Laboratory of Pharmacotherapy of Life-Style Related Diseases, Graduate School of Pharmaceutical Sciences, Tohoku University, Aoba, Aramaki, Aoba-ku, Sendai 980-8578, Japan Tel: +81 22 795 5503; fax: +81 22 795 5504; e-mail: [email protected] Received 21 October 2009 Accepted 4 May 2010 Pharmacogenetics and Genomics: July 2010 - Volume 20 - Issue 7 - p 459-462 doi: 10.1097/FPC.0b013e32833bba0e Buy Metrics 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. © 2010 Lippincott Williams & Wilkins, Inc.