Development of a genotyping tool for a functionally relevant CYP2C19 allele (Phe100Asn, Ala103Val and Ile112Leu) in cynomolgus macaques

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.