Frequencies of CYP2D6 mutant alleles in a normal Japanese population and metabolic activity of dextromethorphan O-demethylation in different CYP2D6 genotypes.
OBJECTIVE
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 metabolic 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 subjects were phenotyped with dextromethorphan.


RESULTS
The frequencies of CYP2D6*2,*5, *10 and *14 were 12.9, 6.2, 38.6 and 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 dextromethorphan in subjects with genotypes predicting intermediate metabolizers was significantly 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 than previously thought for the treatment of Japanese patients with drugs metabolized by CYP2D6.
Kubota
T
T
Research Testing Department, SRL Inc., Hachioji-shi, Tokyo, Japan.
Yamaura
Y
Y
Ohkawa
N
N
Hara
H
H
Chiba
K
K
D000328:Adult; D000483:Alleles; D044466:Asian People / Q000235:genetics*; D019389:Cytochrome P-450 CYP2D6 / Q000235:genetics* / Q000378:metabolism*; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism*; D004247:DNA / Q000032:analysis; D017931:DNA Primers / Q000737:chemistry; D003915:Dextromethorphan / Q000378:metabolism*; D005260:Female; D005787:Gene Frequency; D005838:Genotype; D006801:Humans; D007564:Japan / Q000208:ethnology; D008297:Male; D008875:Middle Aged; D009154:Mutation; D010090:Oxidoreductases, O-Demethylating / Q000378:metabolism*; D010641:Phenotype; D016133:Polymerase Chain Reaction; D012150:Polymorphism, Restriction Fragment Length
D017931:DNA Primers; D003915:Dextromethorphan; D004247:DNA; D003577:Cytochrome P-450 Enzyme System; D010090:Oxidoreductases, O-Demethylating; C052861:dextromethorphan O-demethylase; D019389:Cytochrome P-450 CYP2D6