2021 Volume 65 Issue 1 Pages 1-5
Adenosine triphosphate (ATP)-binding cassette transporter G2 (ABCG2; also known as breast cancer resistance protein, BCRP) is a physiologically important urate transporter of which congenital dysfunction is identified as a strong genetic risk factor of gout as well as hyperuricemia, a common disease characterized by elevated serum urate concentrations. Since uric acid is the final metabolite in the purine catabolic pathway in humans, urate excretion from the body is necessary for the maintenance of uric acid homeostasis. Accumulating evidence suggests that the net amount of excreted uric acid is regulated mainly by urate transporters. Among them, ABCG2 is expressed on the apical membranes of intestinal and renal epithelial cells where it plays a pivotal role in urate excretion from the body as an ATP-dependent urate exporter. Moreover, recent studies show the clinical significance of both common and rare variants of ABCG2, suggesting the importance of further identification and validation of population-specific rare variants of ABCG2 to achieve more effective and accurate prediction of ABCG2-related gout/hyperuricemia risk. Via molecular analyses, we have characterized such ABCG2 variants, which disrupt ABCG2 function as a urate transporter, found in the Japanese population and the Czech Republic population. Additionally, given that ABCG2 is recognized to be an important determinant of pharmacokinetic characteristics of its substrate drugs, such information will also be useful in the field of pharmacogenomics. Here, we would like to introduce our recent findings about pathophysiological importance of ABCG2 that has been investigated through clinico-genetic analyses for gout/hyperuricemia patients in combination with functional studies.