Pharmacokinetics and Bioanalysis Center, Shin Nippon Biomedical Laboratories, Ltd.
Drug Metab Pharmacokinet. 2011;26(6):627-31. doi: 10.2133/dmpk.DMPK-11-NT-026. Epub 2011 Aug 16.
The cytochrome P450 (CYP) 1 family consists of the CYP1A, CYP1B, CYP1C, and CYP1D subfamilies. In humans, CYP1A1, CYP1A2, and CYP1B1 are expressed and encode functional enzymes, whereas CYP1D1P (formerly known as CYP1A8P) is present as a pseudogene as a result of five nonsense mutations in exon 2 and exon 7 of the putative coding region. We previously identified CYP1D1 in macaques and found that it was expressed and functional in liver. Moreover, the nonsense mutations in exon 2 and exon 7 were not found in the 20 cynomolgus macaques and 10 rhesus macaques analyzed in that previous study. These results raised the possibility that CYP1D1 is a functional gene in macaques; however, the possibility that nonsense mutations are present in other exons cannot be excluded. In this study, we sought to identify genetic variants of CYP1D1 in 63 cynomolgus macaques and 30 rhesus macaques; we did not find nonsense mutations in any coding exon of the animals analyzed. Moreover, 15 of the 63 cynomolgus macaques were analyzed by quantitative polymerase chain reaction, confirming hepatic expression of CYP1D1 in all 15 animals. These results suggest that CYP1D1 is most likely functional in cynomolgus macaques and rhesus macaques.
细胞色素 P450 (CYP) 1 家族包括 CYP1A、CYP1B、CYP1C 和 CYP1D 亚家族。在人类中，CYP1A1、CYP1A2 和 CYP1B1 表达并编码功能性酶，而 CYP1D1P（以前称为 CYP1A8P）作为假基因存在，因为在假定的编码区的外显子 2 和外显子 7 中存在五个无意义突变。我们之前在猕猴中鉴定出 CYP1D1，并发现它在肝脏中表达和具有功能。此外，在之前的研究中分析的 20 只食蟹猴和 10 只恒河猴中未发现外显子 2 和外显子 7 中的无意义突变。这些结果提出 CYP1D1 可能是猕猴中的功能性基因的可能性；然而，不能排除无意义突变存在于其他外显子中的可能性。在这项研究中，我们试图在 63 只食蟹猴和 30 只恒河猴中鉴定 CYP1D1 的遗传变异；我们在分析的动物的任何编码外显子中都没有发现无意义突变。此外，对 63 只食蟹猴中的 15 只进行了定量聚合酶链反应分析，证实 CYP1D1 在所有 15 只动物的肝脏中表达。这些结果表明 CYP1D1 很可能在食蟹猴和恒河猴中具有功能。
