Genetic polymorphism of cytochrome P450s, CYP2C19, and CYP2C9 in a Japanese population.
Genotypings of two mutations (*2 and *3) in CYP2C19 and the amino acid variants (Arg144/Cys, Tyr358/Cys, Ile359/Leu, and Gly417/Asp) in CYP2C9 were carried out in 140 unrelated Japanese subjects. Thirty-three subjects (23.6%) were genotypically identified as poor metabolizers of CYP2C19, and the allele frequencies of the CYP2C19*2 and CYP2C19*3 were 0.35 and 0.11, respectively. The authors' findings are in agreement with the 18% to 23% prevalence of poor metabolizers in the Japanese populations previously phenotyped. In CYP2C9, all subjects were homozygous (CYP2C9*1) for Arg144, Tyr358, Ile359, and Gly417, except for five subjects (3.6%) who were heterozygous for the Leu359 (CYP2C9*3). The frequencies of Arg144, Tyr358, Ile359, Leu359, and Gly417 variants were 1.0, 1.0, 0.982, 0.018, and 1.0, respectively. The low frequency of the Cys144 allele (CYP2C9*2) in the Japanese population is different from the frequency recently found in British subjects (allele frequency, 0.125 to 0.192). The results suggest that the known interindividual variations in the CYP2C9 sequence among Japanese subjects is small, and that Ile359/Leu is one possible site showing interracial polymorphism.
Kimura
M
M
Division of Pharmaceutical Sciences, Kyushu University, Kyushu Pharmacology Research Clinic, Fukuoka, Japan.
Ieiri
I
I
Mamiya
K
K
Urae
A
A
Higuchi
S
S
D000328:Adult; D000483:Alleles; D001189:Aryl Hydrocarbon Hydroxylases; D044466:Asian People / Q000235:genetics*; D065731:Cytochrome P-450 CYP2C19; D065729:Cytochrome P-450 CYP2C9; D003577:Cytochrome P-450 Enzyme System / Q000235:genetics*; D005260:Female; D005838:Genotype; D006801:Humans; D007564:Japan / Q000453:epidemiology; D008297:Male; D008875:Middle Aged; D006899:Mixed Function Oxygenases / Q000235:genetics*; D009154:Mutation / Q000235:genetics*; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic; D015995:Prevalence; D039181:Steroid 16-alpha-Hydroxylase; D013250:Steroid Hydroxylases / Q000235:genetics*
D003577:Cytochrome P-450 Enzyme System; D006899:Mixed Function Oxygenases; D013250:Steroid Hydroxylases; C450260:CYP2C9 protein, human; D065729:Cytochrome P-450 CYP2C9; D001189:Aryl Hydrocarbon Hydroxylases; C045793:CYP2C19 protein, human; D065731:Cytochrome P-450 CYP2C19; D039181:Steroid 16-alpha-Hydroxylase