Ethnic differences of the primary gene defect at the cytochrome P-450 2D6

The cytochrome P-450-dependent monooxygenase system is involved in the metabolism of both endogenous compounds and xenobiotics. The role of these enzymes in toxicological response is exemplified by an autosomal recessive polymorphism at the cytochrome P-450 2D6 debrisoquine-4-hydroxylase locus, which results in the severely impaired metabolism of many drugs [Gough et al. (1990) Nature 347: 773-776]. The prevalence of this polymorphism (poor metabolizer) differs considerably between ethnic groups. Here we analyzed the P-450 2D6 polymorphism in 25 Japanese and 20 Chinese by DNA-based genetic assay using peripheral leukocyte. Although the phenotype of all the normal metabolizers and 79% of the poor metabolizers could be identified in Caucasians, this DNA-based genomic assay could not predict poor metabolizers in both the Japanese and Chinese. These results indicate that the genetic mechanism of the phenotyped poor metabolizer in Orientals is different from that in Caucasians.