THE CYP2D6 GENETIC POLYMORPHISM

Debrisquine/Sparteine基因多态是由于突变或缺失 编码细胞色素P450细胞色素P2D6的等位基因。这种多态是大多数 在高加索人中流行，其中7%到10%的人拥有两个零等位基因 不能代谢大量具有重要治疗意义的物质 毒品。已经对几个无效等位基因进行了测序并建立了聚合酶链式反应分析方法 用于诊断目的。超过95%的有缺陷的代谢物可以 经聚合酶链式反应(PCR)诊断。药物代谢的种族间差异也一直是 已经进行了描述和详细的研究，比较了一些 酵素。Debrisquine/Sparteine多态表现出显著 东方题材的不同特点。在日语和汉语中， 缺陷个体的频率从0到最高2.3%不等， 取决于目标人群和用于表型鉴定的药物。一个 最耐人寻味的观察是，新陈代谢的平均速度 不同民族的正常代谢物不同；东方受试者 平均而言，与高加索人相比，当司马汀、 以CYP2D6底物为探针药物对其进行了研究。 不同。对几个CYP2D6等位基因进行了测序 一种新的变异等位基因，命名为CYP2D6v1 发现含有两种氨基酸变化，可能会降低 新陈代谢速度。此外，还有几个CYP2D6D零等位基因和两个 发现了CYP2D6B突变体。后一项发现表明，CYP2D6B 等位基因并不是高加索人独有的。

The debrisoquine/sparteine genetic polymorphism is due to mutant or null alleles encoding the cytochrome P450 CYP2D6. This polymorphism is most prevalent in Caucasians in which 7 to 10% possess two null alleles and are incapable of metabolizing a large number of therapeutically-important drugs. Several null alleles have been sequenced and PCR assays developed for diagnostic purposes. Over 95% of deficient metabolizers can be diagnosed by PCR. Interethnic variation of drug metabolism has also been described and detailed studies have been conducted comparing a number of enzymes. The debrisoquine/sparteine polymorphism exhibits markedly different characteristics in Oriental subjects. In Japanese and Chinese, the frequency of deficient individuals ranges from 0 to a maximum of 2.3%, depending on the target population and the drug used for phenotyping. A most intriguing observation is that the average rate of metabolism among the normal metabolizers differ between ethnic groups; Oriental subjects have, on average, a slower metabolism than Caucasians when sparteine, a CYP2D6 substrate, was used as the probe drug to investigate this difference. Several CYP2D6 alleles were sequenced from a population of Japanese subjects and a new variant allele, designated CYP2D6v1 was uncovered that contains two amino acid changes that might confer lower rates of metabolism. In addition several CYP2D6D null alleles and two CYP2D6B mutants were found. The latter finding indicates that the CYP2D6B allele is not exclusive to Caucasians.