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dc.contributor.authorHoque, K.M.
dc.contributor.authorDixon, E.E.
dc.contributor.authorLewis, R.M.
dc.contributor.authorWoodward, O.M.
dc.contributor.authorHalperin Kuhns, V.en_US
dc.date.accessioned2020-06-08T20:20:57Z
dc.date.available2020-06-08T20:20:57Z
dc.date.issued2020
dc.identifier.urihttps://www.scopus.com/inward/record.uri?eid=2-s2.0-85085700363&doi=10.1038%2fs41467-020-16525-w&partnerID=40&md5=d929a47189126b4d13cc8a631189b31c
dc.identifier.urihttp://hdl.handle.net/10713/12976
dc.description.abstractThe pathophysiological nature of the common ABCG2 gout and hyperuricemia associated variant Q141K (rs2231142) remains undefined. Here, we use a human interventional cohort study (ACTRN12615001302549) to understand the physiological role of ABCG2 and find that participants with the Q141K ABCG2 variant display elevated serum urate, unaltered FEUA, and significant evidence of reduced extra-renal urate excretion. We explore mechanisms by generating a mouse model of the orthologous Q140K Abcg2 variant and find male mice have significant hyperuricemia and metabolic alterations, but only subtle alterations of renal urate excretion and ABCG2 abundance. By contrast, these mice display a severe defect in ABCG2 abundance and function in the intestinal tract. These results suggest a tissue specific pathobiology of the Q141K variant, support an important role for ABCG2 in urate excretion in both the human kidney and intestinal tract, and provide insight into the importance of intestinal urate excretion for serum urate homeostasis. Copyright 2020, The Author(s).en_US
dc.description.sponsorshipTh Baltimore PKD Research and Clinical Core Center for providing normal human kidney cells and tissues. The work of O.M.W. was supported by NIDDK grants R01DK114091 and 5P30DK090868.en_US
dc.description.urihttp://doi.org/10.1038/s41467-020-16525-wen_US
dc.language.isoen_USen_US
dc.publisherNature Researchen_US
dc.relation.ispartofNature Communications
dc.subject.meshGout--geneticsen_US
dc.subject.meshGout--physiopathologyen_US
dc.titleThe ABCG2 Q141K hyperuricemia and gout associated variant illuminates the physiology of human urate excretionen_US
dc.typeArticleen_US
dc.identifier.doi10.1038/s41467-020-16525-w


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