PT  - JOURNAL ARTICLE
AU  - Kanako Sakuyama
AU  - Takamitsu Sasaki
AU  - Shuta Ujiie
AU  - Kanako Obata
AU  - Michinao Mizugaki
AU  - Masaaki Ishikawa
AU  - Masahiro Hiratsuka
TI  - Functional Characterization of 17 <em>CYP2D6</em> Allelic Variants (CYP2D6.2, 10, 14A–B, 18, 27, 36, 39, 47–51, 53–55, and 57)
AID  - 10.1124/dmd.108.023242
DP  - 2008 Dec 01
TA  - Drug Metabolism and Disposition
PG  - 2460--2467
VI  - 36
IP  - 12
4099  - http://dmd.aspetjournals.org/content/36/12/2460.short
4100  - http://dmd.aspetjournals.org/content/36/12/2460.full
SO  - Drug Metab Dispos2008 Dec 01; 36
AB  - Cytochrome P450 2D6 (CYP2D6) is an enzyme of potential importance for the metabolism of drugs used clinically, and it exhibits genetic polymorphism with interindividual differences in metabolic activity. To date, 21 CYP2D6 allelic variants have been identified in the Japanese population. The aim of this study was to investigate the functional characterization of CYP2D6 variants identified in Japanese subjects. Wild-type CYP2D6 and its variants, namely, CYP2D6.2, CYP2D6.10, CYP2D6.14A, CYP2D6.14B, CYP2D6.18, CYP2D6.27, CYP2D6.36, CYP2D6.39, CYP2D6.47, CYP2D6.48, CYP2D6.49, CYP2D6.50, CYP2D6.51, CYP2D6.53, CYP2D6.54, CYP2D6.55, and CYP2D6.57 were transiently expressed in COS-7 cells, and enzymatic activities of the CYP2D6 variant proteins were characterized using bufuralol and dextromethorphan. Functional characterization of 17 CYP2D6 variants revealed an absence of enzyme activity in four (CYP2D6.14A, CYP2D6.36, CYP2D6.47, and CYP2D6.57), low activity in eight (CYP2D6.10, CYP2D6.14B, CYP2D6.18, CYP2D6.49, CYP2D6.50, CYP2D6.51, CYP2D6.54, and CYP2D6.55), and high activity in one (CYP2D6.53) compared with the wild type. Analysis of CYP2D6 variant proteins can be useful for predicting CYP2D6 phenotypes and could be applied to personalized drug therapy. The American Society for Pharmacology and Experimental Therapeutics