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

In cynomolgus macaques, which are widely used in drug metabolism studies, CYP2C19(formerly known as CYP2C75) is abundantly expressed in liver, metabolizes human CYP2Csubstrates and is thus an important drug-metabolizing enzyme. One of the cynomolgusCYP2C19 alleles (p.Phe100Asn, p.Ala103Val and p.Ile112Leu) results insubstantially reduced metabolic activity and thus is an important allele in drugmetabolism studies. For this allele, a genotyping tool was developed using allele-specificTaqMan probe. Genotyping 40 Cambodian cynomolgus macaques using this tool found 1homozygote, 17 heterozygotes and 22 wild type animals, and the result was confirmed bydirect-sequencing. Interestingly, this allele frequency was similar to that of Chinesecynomolgus macaques. The genotyping tool established is useful for drug metabolism studiesusing cynomolgus macaques.