Ethnic Differences in ATP-binding Cassette Transporter, Sub-family G, Member 2 (ABCG2/BCRP): Genotype Combinations and Estimated Functions

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Author(s)

    • SAKIYAMA Masayuki
    • Department of Integrative Physiology and Bio-Nano Medicine, National Defense Medical College|Department of Dermatology, National Defense Medical College
    • SHINOMIYA Nariyoshi
    • Department of Integrative Physiology and Bio-Nano Medicine, National Defense Medical College
    • MATSUO Hirotaka
    • Department of Integrative Physiology and Bio-Nano Medicine, National Defense Medical College
    • TAKADA Yuzo
    • The Central Research Institute, National Defense Medical College
    • NAKAYAMA Akiyoshi
    • Department of Integrative Physiology and Bio-Nano Medicine, National Defense Medical College
    • TAKADA Tappei
    • Department of Pharmacy, The University of Tokyo Hospital, Faculty of Medicine, The University of Tokyo
    • KITAJIRI Shin-ichiro
    • Department of Otolaryngology, Head and Neck Surgery, Graduate School of Medicine, Kyoto University
    • WAKAI Kenji
    • Department of Preventive Medicine, Nagoya University Graduate School of Medicine
    • SUZUKI Hiroshi
    • Department of Pharmacy, The University of Tokyo Hospital, Faculty of Medicine, The University of Tokyo

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 <i>ABCG2</i> dysfunctional diplotypes were commonly observed in both Caucasians (16.5%) and African-Americans (16.0%), the genotyping of the two <i>ABCG2</i> 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.

Journal

  • Drug Metabolism and Pharmacokinetics

    Drug Metabolism and Pharmacokinetics 29(6), 490-492, 2014

    The Japanese Society for the Study of Xenobiotics

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