Kimura M, Ieiri I, Mamiya K, Urae A, Higuchi S
Division of Pharmaceutical Sciences, Kyushu University, Kyushu Pharmacology Research Clinic, Fukuoka, Japan.
Ther Drug Monit. 1998 Jun;20(3):243-7. doi: 10.1097/00007691-199806000-00001.
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 CYP2C192 and CYP2C193 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 (CYP2C91) for Arg144, Tyr358, Ile359, and Gly417, except for five subjects (3.6%) who were heterozygous for the Leu359 (CYP2C93). 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.
对140名无亲缘关系的日本受试者进行了CYP2C19中两个突变（2和3）以及CYP2C9中氨基酸变体（Arg144/Cys、Tyr358/Cys、Ile359/Leu和Gly417/Asp）的基因分型。33名受试者（23.6%）在基因分型上被鉴定为CYP2C19慢代谢者，CYP2C192和CYP2C193的等位基因频率分别为0.35和0.11。作者的研究结果与之前已进行表型分析的日本人群中18%至23%的慢代谢者患病率一致。在CYP2C9中，除了5名（3.6%）Leu359杂合（CYP2C93）的受试者外，所有受试者的Arg144、Tyr358、Ile359和Gly417均为纯合（CYP2C91）。Arg144、Tyr358、Ile359、Leu359和Gly417变体的频率分别为1.0、1.0、0.982、0.018和1.0。日本人群中Cys144等位基因（CYP2C9*2）的低频率与最近在英国受试者中发现的频率（等位基因频率为0.125至0.192）不同。结果表明，日本受试者中已知的CYP2C9序列个体间变异较小，且Ile359/Leu是一个可能表现出种族间多态性的位点。
