正常日本人群中CYP2D6突变等位基因的频率以及不同CYP2D6基因型中右美沙芬O-去甲基化的代谢活性。
Frequencies of CYP2D6 mutant alleles in a normal Japanese population and metabolic activity of dextromethorphan O-demethylation in different CYP2D6 genotypes.
作者信息
Kubota T, Yamaura Y, Ohkawa N, Hara H, Chiba K
机构信息
Research Testing Department, SRL Inc., Hachioji-shi, Tokyo, Japan.
出版信息
Br J Clin Pharmacol. 2000 Jul;50(1):31-4. doi: 10.1046/j.1365-2125.2000.00209.x.
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. CYP2D63, *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
CYP2D65 and CYP2D614 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.
目的
确定11种CYP2D6突变等位基因（CYP2D6*2、*3、*4、*5、*8、*10、*11、*12、*14、17和18）的频率，以及它们与日本人群中CYP2D6代谢能力的关系。
方法
采用聚合酶链反应扩增法对162名无亲缘关系的健康日本受试者进行基因分型，并用右美沙芬对35名受试者进行表型分析。
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CYP2D63、*4、*8、*11、*12、17和18。预测为中间代谢型的受试者中右美沙芬的平均对数代谢率显著高于功能等位基因和缺陷等位基因杂合子的平均对数代谢率。
结论
CYP2D65和CYP2D614是在日本受试者中发现的主要缺陷等位基因。此外，对于CYP2D6代谢的药物治疗日本患者，CYP2D6*10可能比以前认为的发挥更重要的作用。
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