Polymorphisms of cytochrome P450 2B6 (CYP2B6) in cynomolgus and rhesus macaques

Journal of Medical Primatology
Yasuhiro UnoH Yamazaki

Abstract

Cytochrome P450 2B6 (CYP2B6) is an important drug-metabolizing enzyme and is expressed in liver. Although human CYP2B6 variants account for variable enzyme properties among individuals and populations, CYP2B6 genetic variants have not been investigated in cynomolgus macaques, widely used in drug metabolism studies. CYP2B6 was resequenced in 120 cynomolgus macaques and 23 rhesus macaques by direct sequencing. Twenty-three non-synonymous variants were found, of which 12 and 3 were unique to cynomolgus macaques and rhesus macaques, respectively. By functional characterization using the 14 variant proteins, 8 variants (V114I, R253C, M435I, V459M, L465P, C475S, R487C, and R487H) showed different rate (>1.5-fold) of testosterone 16β-hydroxylation to wild type. However, the four variants (M435I, L465P, C475S, and R487H) were analyzed in liver microsomes, and the catalytic rates were not substantially different from wild type. Macaque CYP2B6 was polymorphic, and the genotype could partly account for variable enzyme activities of macaque CYP2B6.

References

Jun 11, 2004·The Journal of Pharmacology and Experimental Therapeutics·Thomas LangUlrich M Zanger
Oct 1, 2008·Drug Metabolism and Disposition : the Biological Fate of Chemicals·Yasuhiro UnoRyoichi Nagata
Nov 17, 2009·Drug Metabolism and Disposition : the Biological Fate of Chemicals·Yasuhiro UnoHiroshi Yamazaki
Jan 5, 2010·The Journal of Veterinary Medical Science·Yasuhiro UnoHiroshi Yamazaki
Jun 10, 2011·Basic & Clinical Pharmacology & Toxicology·Yasuhiro UnoHiroshi Yamazaki
Aug 19, 2011·The Journal of Pharmacology and Experimental Therapeutics·Shotaro UeharaYasuhiro Uno
Nov 30, 2011·Drug Metabolism and Pharmacokinetics·Shotaro UeharaYasuhiro Uno
Oct 17, 2014·Drug Metabolism and Disposition : the Biological Fate of Chemicals·Shinya HosakaHiroshi Yamazaki
Aug 1, 2015·Drug Metabolism and Disposition : the Biological Fate of Chemicals·Shotaro UeharaHiroshi Yamazaki
Jul 16, 2016·Biopharmaceutics & Drug Disposition·Kazuhide IwasakiHiroshi Yamazaki

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