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Polymorphisms of cytochrome P450 2B6 ( CYP 2B6 ) in cynomolgus and rhesus macaques
Author(s) -
Uno Yasuhiro,
Uehara Shotaro,
Yamazaki Hiroshi
Publication year - 2018
Publication title -
journal of medical primatology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.31
H-Index - 42
eISSN - 1600-0684
pISSN - 0047-2565
DOI - 10.1111/jmp.12336
Subject(s) - macaque , rhesus macaque , cytochrome p450 , genotype , biology , hydroxylation , cyp2d6 , enzyme , genetics , microbiology and biotechnology , biochemistry , gene , paleontology
Background Cytochrome P450 2B6 ( CYP 2B6) is an important drug‐metabolizing enzyme and is expressed in liver. Although human CYP 2B6 variants account for variable enzyme properties among individuals and populations, CYP 2B6 genetic variants have not been investigated in cynomolgus macaques, widely used in drug metabolism studies. Methods CYP 2B6 was resequenced in 120 cynomolgus macaques and 23 rhesus macaques by direct sequencing. Results 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. Conclusions Macaque CYP 2B6 was polymorphic, and the genotype could partly account for variable enzyme activities of macaque CYP 2B6.