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Drug Metab Pharmacokinet. 2011;26(6):627-31. doi: 10.2133/dmpk.DMPK-11-NT-026. Epub 2011 Aug 16.

Discovery of genetic variants in CYP1D1: implication for functional integrity of CYP1D1 in cynomolgus macaques and rhesus macaques.

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1
Pharmacokinetics and Bioanalysis Center, Shin Nippon Biomedical Laboratories, Ltd.

Abstract

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.

PMID:
21844658
[Indexed for MEDLINE]
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