THE CYP2D6 GENETIC POLYMORPHISM

异喹胍/鹰爪豆碱遗传多态性是由于突变或无效 编码细胞色素P450 CYP 2D 6的等位基因。 这种多态性是最 在高加索人中流行，其中7 - 10%具有两个无效等位基因， 不能代谢大量的治疗上重要的 毒品 几个无效等位基因已经测序和PCR检测开发 用于诊断目的。 超过95%的代谢缺陷者可以 PCR诊断 药物代谢的种族间差异也被认为是 已经进行了描述和详细的研究， 内切酶 异喹胍/鹰爪豆碱多态性显著地表现出 东方人的不同特点。 在日语和汉语中， 缺陷个体的频率范围从0到最大2.3%， 这取决于目标人群和用于表型分析的药物。 一 最有趣的观察是， 正常代谢者在种族群体之间不同;东方受试者 平均来说，当金雀花碱，一种 使用CYP 2D 6底物作为探针药物来研究这一点 差 从一个人群中测序了几个CYP 2D 6等位基因， 日本受试者和一个新的变异等位基因，命名为CYP 2D 6v 1， 发现含有两个氨基酸的变化，可能会降低 代谢率。 此外，几个CYP 2D 6D无效等位基因和两个 发现CYP 2D 6 B突变体，后者的发现表明CYP 2D 6 B 等位基因并不是白种人独有的。

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.