Frequencies of CYP2D6 mutant alleles in a normal Japanese population and metabolic activity of dextromethorphan O-demethylation in different CYP2D6 genotypes
Frequencies of CYP2D6 mutant alleles in a normal Japanese population and metabolic activity of dextromethorphan O-demethylation in different CYP2D6 genotypes
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DOI：
10.1046/j.1365-2125.2000.00209.x
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发表时间：
2000-07-01
影响因子：
3.4
通讯作者：
Chiba, K
中科院分区：
文献类型：
--
作者：
Kubota, T;Yamaura, Y;Chiba, K
目的 确定日本受试者中 11 个 CYP2D6 突变等位基因（CYP2D6*2、*3、*4、*5、*8、*10、*11、*12、*14、*17 和 *18）的频率及其与 CYP2D6 代谢能力的关系。 方法 采用聚合酶链式反应扩增方法对 162 名无血缘关系的健康日本受试者进行基因分型，并分析其与 CYP2D6 代谢能力的关系。 35 名受试者用右美沙芬进行了表型分析。结果 在我们的日本受试者中，CYP2D6*2、*5、*10 和 *14 的频率分别为 12.9%、6.2%、38.6% 和 2.2%。未检测到 CYP2D6*3、*4、*8、*11、*12、*17 和 *18。在具有预测中间代谢者基因型的受试者中，右美沙芬的平均对数代谢比显着大于功能性和缺陷等位基因的杂合子。结论 CYP2D6*5 和 CYP2D6*14 是在日本受试者中发现的主要缺陷等位基因。此外，对于使用CYP2D6代谢的药物治疗日本患者来说，CYP2D6*10可能发挥比之前想象的更重要的作用。
Aims 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.