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

https://doi.org/10.2133/dmpk.DMPK-14-SC-041Get rights and content

Summary:

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.

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This study was supported by grants from the Ministry of Education, Culture, Sports, Science and Technology (MEXT) of Japan, including the MEXT KAKENHI (grant numbers 221S0002, 25293145, 22689021, 25670307), the Ministry of Health, Labour and Welfare of Japan, the Ministry of Defense of Japan, the Japan Society for the Promotion of Science, the Takeda Science Foundation, the AstraZeneca VRI Research Grant, the Kawano Masanori Memorial Foundation for Promotion of Pediatrics, and the Gout Research Foundation of Japan.

Masayuki Sakiyama and Hirotaka Matsuo contributed equally to this work.

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