Comparison of the polymorphic regions of the cytochrome P450CYP2E1 gene ofhumans and patas and cynomolgus monkeys

Cytochrome P450 2E1 (CYP2E1) metabolizes low molecular weight toxicants. CY P2EI gene polymorphisms have been linked to risk of various cancers and liv er disease in humans. Since the patas monkey is a promising model for study of cancer-related alcohol/nitrosamine interactions, we examined CYP2EI in this monkey for characteristics of two regions that are polymorphic in huma ns, an RsaI site in the 5' promoter region and a DraI site in intron 6, Ano ther monkey species often used in biomedical research, the cynomolgus monke y, was also examined. Human DNA primers used to amplify a 413 bp segment ar ound the RsaI site also amplified a segment of similar size (409 bp) from D NA of 25 patas monkeys, whereas a product of similar to 800 bp was amplifie d from DNA of eight cynomolgus monkeys. RsaI did not cut the amplified DNA product from either monkey species. Sequencing revealed that the patas RsaI site was identical to that in humans with the c2c2 CYP2E1 genotype, GTAT, The equivalent cynomolgus sequence, CTAC, has not been observed in humans. Thus, the patas monkey appears to be a useful model for CYP2E1 c2c2 humans, and this genotype, present in 2-25% of humans, may be more primitive than c1c1, For the DraI site, the human primers amplified DNA products similar i n size to those from humans, from all patas and cynomolgus monkey DNA sampl es; none mere cut by DraI, Thus, both monkey species appeared to be general ly similar to humans of CYP2E1 CC DraI genotype, which is the rarer form of the gene.