Development of a genotyping tool for a functionally relevant
CYP2C19 allele (Phe100Asn,Ala103Val and Ile112Leu) in cynomolgus
macaques |
| |
Authors: | Yasuhiro UNO Hiroshi YAMAZAKI |
| |
Institution: | 1)Pharmacokinetics and Bioanalysis Center, Shin Nippon Biomedical Laboratories, Ltd., Kainan, Wakayama 642–0017, Japan;2)Laboratory of Drug Metabolism and Pharmacokinetics, Showa Pharmaceutical University, Machida, Tokyo 194–8543, Japan |
| |
Abstract: | In cynomolgus macaques, which are widely used in drug metabolism studies, CYP2C19
(formerly known as CYP2C75) is abundantly expressed in liver, metabolizes human CYP2C
substrates and is thus an important drug-metabolizing enzyme. One of the cynomolgus
CYP2C19 alleles (p.Phe100Asn, p.Ala103Val and p.Ile112Leu) results in
substantially reduced metabolic activity and thus is an important allele in drug
metabolism studies. For this allele, a genotyping tool was developed using allele-specific
TaqMan probe. Genotyping 40 Cambodian cynomolgus macaques using this tool found 1
homozygote, 17 heterozygotes and 22 wild type animals, and the result was confirmed by
direct-sequencing. Interestingly, this allele frequency was similar to that of Chinese
cynomolgus macaques. The genotyping tool established is useful for drug metabolism studies
using cynomolgus macaques. |
| |
Keywords: | CYP2C19 cytochrome P450 genotyping monkey polymorphisms |
|
|