{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,14]],"date-time":"2026-10-14T11:46:14Z","timestamp":1791978374092,"version":"4.4.0"},"reference-count":30,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2014,12,27]],"date-time":"2014-12-27T00:00:00Z","timestamp":1419638400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/3.0\/"}],"funder":[{"DOI":"10.13039\/501100001700","name":"Ministry of Education, Culture, Sports, Science, and Technology","doi-asserted-by":"publisher","award":["221S0002"],"award-info":[{"award-number":["221S0002"]}],"id":[{"id":"10.13039\/501100001700","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001700","name":"Ministry of Education, Culture, Sports, Science, and Technology","doi-asserted-by":"publisher","award":["25293145"],"award-info":[{"award-number":["25293145"]}],"id":[{"id":"10.13039\/501100001700","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001700","name":"Ministry of Education, Culture, Sports, Science, and Technology","doi-asserted-by":"publisher","award":["22689021"],"award-info":[{"award-number":["22689021"]}],"id":[{"id":"10.13039\/501100001700","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001700","name":"Ministry of Education, Culture, Sports, Science, and Technology","doi-asserted-by":"publisher","award":["25670307"],"award-info":[{"award-number":["25670307"]}],"id":[{"id":"10.13039\/501100001700","id-type":"DOI","asserted-by":"publisher"}]},{"name":"the AstraZeneca VRI Research Grant"},{"name":"the Gout Research Foundation of Japan"},{"DOI":"10.13039\/501100001691","name":"the Japan Society for the Promotion of Science","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"crossref"}]},{"name":"the Kawano Masanori Memorial Foundation for Promotion of Pediatrics"},{"name":"the Ministry of Health, Labour and Welfare of Japan"},{"DOI":"10.13039\/100007449","name":"the Takeda Science Foundation","doi-asserted-by":"crossref","id":[{"id":"10.13039\/100007449","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Arthritis &amp; Rheumatology"],"published-print":{"date-parts":[[2015,1]]},"abstract":"<jats:sec><jats:title>Objective<\/jats:title><jats:p>Serum uric acid (SUA) levels in humans are mainly regulated by urate transporters. Recent genome\u2010wide association studies suggested that common variants of the human sodium\u2010dependent phosphate cotransporter type 1 gene (<jats:italic>NPT1\/SLC17A1<\/jats:italic>) influence SUA. NPT1 has been reported to mediate urate transport, but its physiologic role in regulating SUA in humans remains unclear. Furthermore, the findings of replication studies of the relationship between <jats:italic>NPT1<\/jats:italic> variants and gout have been inconsistent. The aims of this study were to investigate the effect of NPT1 on gout and to determine its physiologic role.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Five hundred forty\u2010five male Japanese patients with gout and 1,115 male Japanese control subjects were genotyped for rs1165196 (I269T), a common missense variant in <jats:italic>NPT1<\/jats:italic>. Analyses of the association between rs1165196 and gout were then conducted, focusing especially on renal underexcretion (RUE) gout. Immunohistochemical analysis and functional analysis using <jats:italic>Xenopus<\/jats:italic> oocytes were also performed.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Single\u2010nucleotide polymorphism rs1165196 significantly decreased the risk of RUE gout (odds ratio 0.73, <jats:italic>P<\/jats:italic> = 0.031) but did not confer a risk for all gout (<jats:italic>P<\/jats:italic> = 0.123). The immunohistochemical analysis revealed that human NPT1 is localized to the apical membrane of the renal proximal tubule. The functional analysis using <jats:italic>Xenopus<\/jats:italic> oocyte expression systems showed that rs1165196 increases NPT1\u2010mediated urate export.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>This study showed that NPT1 is a urate exporter located in the renal proximal tubule in humans, and that its common gain\u2010of\u2010function variant, rs1165196, causes RUE gout, a major subtype of gout. These findings enable us to deepen our understanding of the physiologic role of NPT1 as a renal urate exporter as well as its pathophysiologic role in gout.<\/jats:p><\/jats:sec>","DOI":"10.1002\/art.38884","type":"journal-article","created":{"date-parts":[[2014,9,23]],"date-time":"2014-09-23T10:36:02Z","timestamp":1411468562000},"page":"281-287","source":"Crossref","is-referenced-by-count":85,"title":["NPT1\/SLC17A1 Is a Renal Urate Exporter in Humans and Its Common Gain\u2010of\u2010Function Variant Decreases the Risk of Renal Underexcretion Gout"],"prefix":"10.1002","volume":"67","author":[{"given":"Toshinori","family":"Chiba","sequence":"first","affiliation":[{"name":"National Defense Medical College Tokorozawa Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hirotaka","family":"Matsuo","sequence":"additional","affiliation":[{"name":"National Defense Medical College Tokorozawa 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