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Drug Metab Pharmacokinet. 2014;29(6):490-2. doi: 10.2133/dmpk.DMPK-14-SC-041. Epub 2014 May 27.

Ethnic differences in ATP-binding cassette transporter, sub-family G, member 2 (ABCG2/BCRP): genotype combinations and estimated functions.

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1
Department of Integrative Physiology and Bio-Nano Medicine, National Defense Medical College, Tokorozawa, Japan; Department of Dermatology, National Defense Medical College, Tokorozawa, Japan.

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.

PMID:
24869748
DOI:
10.2133/dmpk.DMPK-14-SC-041
[Indexed for MEDLINE]
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