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食蟹猴中一种功能相关的CYP2C19等位基因(Phe100Asn、Ala103Val和Ile112Leu)基因分型工具的开发。

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

作者信息

Uno Yasuhiro, Yamazaki Hiroshi

机构信息

Pharmacokinetics and Bioanalysis Center, Shin Nippon Biomedical Laboratories, Ltd., Kainan, Wakayama 642-0017, Japan.

出版信息

J Vet Med Sci. 2016 Jan;78(1):147-8. doi: 10.1292/jvms.15-0416. Epub 2015 Aug 21.

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.

摘要

食蟹猴广泛应用于药物代谢研究,其肝脏中大量表达CYP2C19(以前称为CYP2C75),可代谢人类CYP2C底物,因此是一种重要的药物代谢酶。食蟹猴的一个CYP2C19等位基因(p.Phe100Asn、p.Ala103Val和p.Ile112Leu)导致代谢活性大幅降低,因此是药物代谢研究中的一个重要等位基因。针对该等位基因,使用等位基因特异性TaqMan探针开发了一种基因分型工具。使用该工具对40只柬埔寨食蟹猴进行基因分型,发现1只纯合子、17只杂合子和22只野生型动物,结果通过直接测序得到证实。有趣的是,该等位基因频率与中国食蟹猴相似。所建立的基因分型工具可用于食蟹猴的药物代谢研究。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6f01/4751135/abfb6e8a77f1/jvms-78-147-g001.jpg

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