Frequencies of CYP2D6 mutant alleles in a normal Japanese population and metabolic activity of dextromethorphan O-demethylation in different CYP2D6 genotypes

Aims To determine the frequencies of 11 CYP2D6 mutant alleles (CYP2D6*2, *3 , *4, *5, *8, *10, *11, *12, *14, *17 and *18), and their relation to the m etabolic capacity of CYP2D6 in Japanese subjects. Methods One hundred and sixty-two unrelated healthy Japanese subjects were genotyped with the polymerase chain reaction amplification method and 35 su bjects were phenotyped with dextromethorphan. Results The frequencies of CYP2D6*2,*5, *10 and *14 were 12.9, 6.2, 38.6 an d 2.2% in our Japanese subjects, respectively. CYP2D6*3, *4, *8, *11, *12, *17 and *18 were not detected. The mean log metabolic ratio of dextromethor phan in subjects with genotypes predicting intermediate metabolizers was si gnificantly greater than that of heterozygotes for functional and defective alleles. Conclusions CYP2D6*5 and CYP2D6*14 are the major defective alleles found in Japanese subjects. In addition, CYP2D6*10 may play a more important role t han previously thought for the treatment of Japanese patients with drugs me tabolized by CYP2D6.