Genetic polymorphism of cytochrome P450s, CYP2C19, and CYP2C9 in a Japanese population

Genotypings of two mutations (*2 and *3) in CY72C19 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.