Ozawa Shogo, Soyama Akiko, Saeki Mayumi, Fukushima-Uesaka Hiromi, Itoda Masaya, Koyano Satoru, Sai Kimie, Ohno Yasuo, Saito Yoshiro, Sawada Jun-Ichi
Division of Pharmacology, National Institute of Health Sciences, Tokyo.
Drug Metab Pharmacokinet. 2004 Apr;19(2):83-95. doi: 10.2133/dmpk.19.83.
Metabolic capacities for debrisoquin, sparteine, mephenytoin, nifedipine, and midazolam, which are substrates of polymorphic CYP2D6, CYP2C19, and CYP3A, have been reported to exhibit, in many cases, remarkable interindividual and ethnic differences. These ethnic differences are partly associated with genetic differences. In the case of the drug transporter ABCB1/MDR1, interindividual differences in its transporter activities toward various clinical drugs are also attributed to several ABCB1/MDR1 genetic polymorphisms. In this review, the existence and frequency of various low-activity alleles of drug metabolizing enzymes as well as populational drug metabolic capacities are compared among several different races or ethnicities. Distribution of nonsynonymous ABCB1/MDR1 SNPs and haplotype frequency in various races are summarized, with the association of nonsynonymous SNPs with large functional alterations as a rare event.
作为多态性CYP2D6、CYP2C19和CYP3A底物的异喹胍、司巴丁、美芬妥英、硝苯地平和咪达唑仑的代谢能力，在许多情况下已被报道存在显著的个体间和种族差异。这些种族差异部分与基因差异有关。就药物转运体ABCB1/MDR1而言，其对各种临床药物的转运体活性的个体间差异也归因于几种ABCB1/MDR1基因多态性。在本综述中，比较了几种不同种族或民族中药物代谢酶各种低活性等位基因的存在情况和频率以及群体药物代谢能力。总结了不同种族中非同义ABCB1/MDR1单核苷酸多态性（SNP）的分布和单倍型频率，非同义SNP与大的功能改变的关联为罕见事件。
