title: Ethnic differences in ATP-binding cassette transporter, sub-family G, member 2 (ABCG2/BCRP): genotype combinations and estimated functions.
abstract: ATP-binding cassette transporter, sub-family G, member 2 (ABCG2/BCRP) is a xenobiotic transporter and also regulates serum uric acid levels as a urate transporter. We have shown that the severity of ABCG2 dysfunction can be estimated by simple genotyping of two dysfunctional variants, Q126X (rs72552713) and Q141K (rs2231142). This genotyping method is widely accepted for the risk analysis of hyperuricemia/gout, but there is no report on ethnic differences in ABCG2 dysfunctions. Here, we estimated ABCG2 dysfunctions by its genotype combination (Q126X and Q141K) and compared them in three different ethnic groups (500 Japanese, 200 Caucasians and 100 African-Americans). The minor allele frequencies of Q126X and Q141K in Japanese (0.025 and 0.275, respectively) were significantly higher than those in Caucasians (0.005 and 0.085, respectively) and African-Americans (0 and 0.090, respectively). Additionally, the rates of mild, moderate and severe ABCG2 dysfunctions in Japanese (35.4%, 12.4% and 1.6%, respectively) were higher than those in Caucasians (14.0%, 2.5% and 0%, respectively) and African-Americans (14.0%, 2.0% and 0%, respectively). Because ABCG2 dysfunctional diplotypes were commonly observed in both Caucasians (16.5%) and African-Americans (16.0%), the genotyping of the two ABCG2 dysfunctional variants is useful for evaluating individual differences in the ABCG2 dysfunction which affect the pharmacokinetics of substrate drugs and hyperuricemia risk in all three ethnic groups.
authors.affiliation: Department of Integrative Physiology and Bio-Nano Medicine, National Defense Medical College, Tokorozawa, Japan; Department of Dermatology, National Defense Medical College, Tokorozawa, Japan.
authors.forename: Masayuki
authors.initials: M
authors.lastname: Sakiyama
authors.forename: Hirotaka
authors.initials: H
authors.lastname: Matsuo
authors.forename: Yuzo
authors.initials: Y
authors.lastname: Takada
authors.forename: Takahiro
authors.initials: T
authors.lastname: Nakamura
authors.forename: Akiyoshi
authors.initials: A
authors.lastname: Nakayama
authors.forename: Tappei
authors.initials: T
authors.lastname: Takada
authors.forename: Shin-Ichiro
authors.initials: S
authors.lastname: Kitajiri
authors.forename: Kenji
authors.initials: K
authors.lastname: Wakai
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Suzuki
authors.forename: Nariyoshi
authors.initials: N
authors.lastname: Shinomiya
mesh_terms: D000070997:ATP Binding Cassette Transporter, Subfamily G, Member 2; D018528:ATP-Binding Cassette Transporters / Q000235:genetics* / Q000378:metabolism; D001741:Black or African American / Q000235:genetics*; D044466:Asian People / Q000235:genetics*; D005787:Gene Frequency; D006239:Haplotypes; D006801:Humans; D033461:Hyperuricemia / Q000208:ethnology / Q000235:genetics / Q000378:metabolism; D007564:Japan / Q000453:epidemiology; D009363:Neoplasm Proteins / Q000235:genetics* / Q000378:metabolism; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide; D012307:Risk Factors; D014527:Uric Acid / Q000378:metabolism; D044465:White People / Q000235:genetics*
chemical_list: C116614:ABCG2 protein, human; D000070997:ATP Binding Cassette Transporter, Subfamily G, Member 2; D018528:ATP-Binding Cassette Transporters; D009363:Neoplasm Proteins; D014527:Uric Acid