title: Ethnic differences in genetic polymorphisms of CYP2D6, CYP2C19, CYP3As and MDR1/ABCB1.
abstract: 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.
authors.affiliation: Division of Pharmacology, National Institute of Health Sciences, Tokyo. sozawa@nihs.go.jp
authors.forename: Shogo
authors.initials: S
authors.lastname: Ozawa
authors.forename: Akiko
authors.initials: A
authors.lastname: Soyama
authors.forename: Mayumi
authors.initials: M
authors.lastname: Saeki
authors.forename: Hiromi
authors.initials: H
authors.lastname: Fukushima-Uesaka
authors.forename: Masaya
authors.initials: M
authors.lastname: Itoda
authors.forename: Satoru
authors.initials: S
authors.lastname: Koyano
authors.forename: Kimie
authors.initials: K
authors.lastname: Sai
authors.forename: Yasuo
authors.initials: Y
authors.lastname: Ohno
authors.forename: Yoshiro
authors.initials: Y
authors.lastname: Saito
authors.forename: Jun-Ichi
authors.initials: J
authors.lastname: Sawada
mesh_terms: D064286:ATP Binding Cassette Transporter 1; D018528:ATP-Binding Cassette Transporters / Q000235:genetics*; D001189:Aryl Hydrocarbon Hydroxylases / Q000235:genetics*; D065731:Cytochrome P-450 CYP2C19; D019389:Cytochrome P-450 CYP2D6 / Q000235:genetics*; D051544:Cytochrome P-450 CYP3A; D005006:Ethnicity; D019450:Genes, MDR / Q000235:genetics*; D006801:Humans; D006899:Mixed Function Oxygenases / Q000235:genetics*; D010084:Oxidation-Reduction; D010089:Oxidoreductases, N-Demethylating / Q000235:genetics*; D011110:Polymorphism, Genetic / Q000235:genetics
chemical_list: D064286:ATP Binding Cassette Transporter 1; D018528:ATP-Binding Cassette Transporters; D006899:Mixed Function Oxygenases; D001189:Aryl Hydrocarbon Hydroxylases; C045793:CYP2C19 protein, human; D065731:Cytochrome P-450 CYP2C19; D019389:Cytochrome P-450 CYP2D6; D051544:Cytochrome P-450 CYP3A; D010089:Oxidoreductases, N-Demethylating