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 (Arg(144)/Cys, Tyr(358)/Cys, Ile(359)/Leu, and Gly(417)/Asp) in CYP2C9 were carried out in 140 unrelated Japanese subjects. Thirty -three subjects (23.6%) were genotypically identified as poor metaboli zers of CYP2C19, and the allele frequencies of the CYP2C192 and CYP2C 193 were 0.35 and 0.11, respectively. The authors' findings are in ag reement with the 18% to 23% prevalence of poor metabolizers in the Jap anese populations previously phenotyped. In CYP2C9, all subjects were homozygous (CYP2C91) for Arg(144), Tyr(358), Ile(359), and Gly(417), except for five subjects (3.6%) who were heterozygous for the Leu(359) , (CYP2C93). The frequencies of Arg(144), Tyr(358), Ile(359), Leu(359 ), and Gly(417), variants were 1.0, 1.0, 0.982, 0.018, and 1.0, respec tively. The low frequency of the Cys(144) allele (CYP2C92) in the Jap anese population is different from the frequency recently found in Bri tish 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 Ile(359)/Leu is one possible sit e showing interracial polymorphism.