{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,14]],"date-time":"2026-09-14T23:36:05Z","timestamp":1789428965799,"version":"build-2803163510"},"reference-count":27,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2016,8,30]],"date-time":"2016-08-30T00:00:00Z","timestamp":1472515200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2016,8,30]],"date-time":"2016-08-30T00:00:00Z","timestamp":1472515200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Sci Rep"],"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    To clarify the physiological and pathophysiological roles of intestinal urate excretion\n                    <jats:italic>via<\/jats:italic>\n                    ABCG2 in humans, we genotyped\n                    <jats:italic>ABCG2<\/jats:italic>\n                    dysfunctional common variants, Q126X (rs72552713) and Q141K (rs2231142), in end-stage renal disease (hemodialysis) and acute gastroenteritis patients, respectively. ABCG2 dysfunction markedly increased serum uric acid (SUA) levels in 106 hemodialysis patients (\n                    <jats:italic>P<\/jats:italic>\n                    \u2009=\u20091.1\u2009\u00d7\u200910\n                    <jats:sup>\u22124<\/jats:sup>\n                    ), which demonstrated the physiological role of ABCG2 for intestinal urate excretion because their urate excretion almost depends on intestinal excretion\n                    <jats:italic>via<\/jats:italic>\n                    ABCG2. Also, ABCG2 dysfunction significantly elevated SUA in 67 acute gastroenteritis patients (\n                    <jats:italic>P<\/jats:italic>\n                    \u2009=\u20096.3\u2009\u00d7\u200910\n                    <jats:sup>\u22123<\/jats:sup>\n                    ) regardless of the degree of dehydration, which demonstrated the pathophysiological role of ABCG2 in acute gastroenteritis. These findings for the first time show ABCG2-mediated intestinal urate excretion in humans, and indicates the physiological and pathophysiological importance of intestinal epithelium as an excretion pathway besides an absorption pathway. Furthermore, increased SUA could be a useful marker not only for dehydration but also epithelial impairment of intestine.\n                  <\/jats:p>","DOI":"10.1038\/srep31003","type":"journal-article","created":{"date-parts":[[2016,8,30]],"date-time":"2016-08-30T05:20:46Z","timestamp":1472534446000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":52,"title":["Hyperuricemia in acute gastroenteritis is caused by decreased urate excretion via ABCG2"],"prefix":"10.1038","volume":"6","author":[{"given":"Hirotaka","family":"Matsuo","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tomoyuki","family":"Tsunoda","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Keiko","family":"Ooyama","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Masayuki","family":"Sakiyama","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tsuyoshi","family":"Sogo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tappei","family":"Takada","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Akio","family":"Nakashima","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Akiyoshi","family":"Nakayama","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Makoto","family":"Kawaguchi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Toshihide","family":"Higashino","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kenji","family":"Wakai","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hiroshi","family":"Ooyama","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ryota","family":"Hokari","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hiroshi","family":"Suzuki","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kimiyoshi","family":"Ichida","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ayano","family":"Inui","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shin","family":"Fujimori","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nariyoshi","family":"Shinomiya","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2016,8,30]]},"reference":[{"key":"BFsrep31003_CR1","doi-asserted-by":"publisher","first-page":"1811","DOI":"10.1056\/NEJMra0800885","volume":"359","author":"DI Feig","year":"2008","unstructured":"Feig, D. I., Kang, D. H. & Johnson, R. J. Uric acid and cardiovascular risk. N. Engl. J. Med. 359, 1811\u20131821 (2008).","journal-title":"N. Engl. J. Med."},{"key":"BFsrep31003_CR2","doi-asserted-by":"publisher","first-page":"5ra11","DOI":"10.1126\/scitranslmed.3000237","volume":"1","author":"H Matsuo","year":"2009","unstructured":"Matsuo, H. et al. Common defects of ABCG2, a high-capacity urate exporter, cause gout: a function-based genetic analysis in a Japanese population. Sci. Transl. Med. 1, 5ra11 (2009).","journal-title":"Sci. Transl. Med."},{"key":"BFsrep31003_CR3","first-page":"3458","volume":"61","author":"M Maliepaard","year":"2001","unstructured":"Maliepaard, M. et al. Subcellular localization and distribution of the breast cancer resistance protein transporter in normal human tissues. Cancer Res. 61, 3458\u20133464 (2001).","journal-title":"Cancer Res."},{"key":"BFsrep31003_CR4","doi-asserted-by":"publisher","first-page":"220","DOI":"10.1038\/sj.ki.5002645","volume":"73","author":"M Huls","year":"2008","unstructured":"Huls, M. et al. The breast cancer resistance protein transporter ABCG2 is expressed in the human kidney proximal tubule apical membrane. Kidney Int. 73, 220\u2013225 (2008).","journal-title":"Kidney Int."},{"key":"BFsrep31003_CR5","doi-asserted-by":"publisher","first-page":"10338","DOI":"10.1073\/pnas.0901249106","volume":"106","author":"OM Woodward","year":"2009","unstructured":"Woodward, O. M. et al. Identification of a urate transporter, ABCG2, with a common functional polymorphism causing gout. Proc. Natl. Acad. Sci. USA 106, 10338\u201310342 (2009).","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"BFsrep31003_CR6","doi-asserted-by":"publisher","first-page":"2014","DOI":"10.1038\/srep02014","volume":"3","author":"H Matsuo","year":"2013","unstructured":"Matsuo, H. et al. Common dysfunctional variants in ABCG2 are a major cause of early-onset gout. Sci. Rep. 3, 2014 (2013).","journal-title":"Sci. Rep."},{"key":"BFsrep31003_CR7","doi-asserted-by":"publisher","first-page":"5227","DOI":"10.1038\/srep05227","volume":"4","author":"A Nakayama","year":"2014","unstructured":"Nakayama, A. et al. Common dysfunctional variants of ABCG2 have stronger impact on hyperuricemia progression than typical environmental risk factors. Sci. Rep. 4, 5227 (2014).","journal-title":"Sci. Rep."},{"key":"BFsrep31003_CR8","doi-asserted-by":"publisher","first-page":"764","DOI":"10.1038\/ncomms1756","volume":"3","author":"K Ichida","year":"2012","unstructured":"Ichida, K. et al. Decreased extra-renal urate excretion is a common cause of hyperuricemia. Nat. Commun. 3, 764 (2012).","journal-title":"Nat. Commun."},{"key":"BFsrep31003_CR9","doi-asserted-by":"publisher","first-page":"3271","DOI":"10.1002\/art.38171","volume":"65","author":"E Krishnan","year":"2013","unstructured":"Krishnan, E. Chronic kidney disease and the risk of incident gout among middle-aged men: a seven-year prospective observational study. Arthritis Rheum. 65, 3271\u20133278 (2013).","journal-title":"Arthritis Rheum."},{"key":"BFsrep31003_CR10","doi-asserted-by":"publisher","first-page":"e27233","DOI":"10.5812\/numonthly.7(3)2015.27233","volume":"7","author":"OS Prasad Sah","year":"2015","unstructured":"Prasad Sah, O. S. & Qing, Y. X. Associations between hyperuricemia and chronic kidney disease: a review. Nephrourol Mon 7, e27233 (2015).","journal-title":"Nephrourol Mon"},{"key":"BFsrep31003_CR11","unstructured":"Sica, D. A. & Schoolwerth, A. In Brenner and Rector\u2019s The Kidney (ed Brenner, B. M. ) 645\u2013649 (Saunders, 2004)."},{"key":"BFsrep31003_CR12","doi-asserted-by":"publisher","first-page":"694","DOI":"10.1002\/art.1780080429","volume":"8","author":"LB Sorensen","year":"1965","unstructured":"Sorensen, L. B. Role of the intestinal tract in the elimination of uric acid. Arthritis Rheum. 8, 694\u2013706 (1965).","journal-title":"Arthritis Rheum."},{"key":"BFsrep31003_CR13","first-page":"211","volume":"136","author":"R Adler","year":"1982","unstructured":"Adler, R., Robinson, R., Pazdral, P. & Grushkin, C. Hyperuricemia in diarrheal dehydration. Am. J. Dis. Child. 136, 211\u2013213 (1982).","journal-title":"Am. J. Dis. Child."},{"key":"BFsrep31003_CR14","doi-asserted-by":"publisher","first-page":"1318","DOI":"10.1056\/NEJM197306212882503","volume":"288","author":"DS Schreiber","year":"1973","unstructured":"Schreiber, D. S., Blacklow, N. R. & Trier, J. S. The mucosal lesion of the proximal small intestine in acute infectious nonbacterial gastroenteritis. N. Engl. J. Med. 288, 1318\u20131323 (1973).","journal-title":"N. Engl. J. Med."},{"key":"BFsrep31003_CR15","doi-asserted-by":"publisher","first-page":"41","DOI":"10.1128\/JVI.76.1.41-57.2002","volume":"76","author":"M Ciarlet","year":"2002","unstructured":"Ciarlet, M., Conner, M. E., Finegold, M. J. & Estes, M. K. Group A rotavirus infection and age-dependent diarrheal disease in rats: a new animal model to study the pathophysiology of rotavirus infection. J. Virol. 76, 41\u201357 (2002).","journal-title":"J. Virol."},{"key":"BFsrep31003_CR16","doi-asserted-by":"publisher","first-page":"10213","DOI":"10.1128\/JVI.78.19.10213-10220.2004","volume":"78","author":"RF Ramig","year":"2004","unstructured":"Ramig, R. F. Pathogenesis of intestinal and systemic rotavirus infection. J. Virol. 78, 10213\u201310220 (2004).","journal-title":"J. Virol."},{"key":"BFsrep31003_CR17","doi-asserted-by":"publisher","first-page":"1939","DOI":"10.1053\/j.gastro.2009.02.076","volume":"136","author":"HB Greenberg","year":"2009","unstructured":"Greenberg, H. B. & Estes, M. K. Rotaviruses: from pathogenesis to vaccination. Gastroenterol. 136, 1939\u20131951 (2009).","journal-title":"Gastroenterol."},{"key":"BFsrep31003_CR18","doi-asserted-by":"publisher","first-page":"206","DOI":"10.1002\/path.4463","volume":"235","author":"SM Karst","year":"2015","unstructured":"Karst, S. M., Zhu, S. & Goodfellow, I. G. The molecular pathology of noroviruses. J. Pathol. 235, 206\u2013216 (2015).","journal-title":"J. Pathol."},{"key":"BFsrep31003_CR19","doi-asserted-by":"publisher","first-page":"e30456","DOI":"10.1371\/journal.pone.0030456","volume":"7","author":"A Hosomi","year":"2012","unstructured":"Hosomi, A., Nakanishi, T., Fujita, T. & Tamai, I. Extra-renal elimination of uric acid via intestinal efflux transporter BCRP\/ABCG2. PLoS One 7, e30456 (2012).","journal-title":"PLoS One"},{"key":"BFsrep31003_CR20","first-page":"1","volume":"52","author":"CK King","year":"2003","unstructured":"King, C. K., Glass, R., Bresee, J. S. & Duggan, C. Managing acute gastroenteritis among children: oral rehydration, maintenance, and nutritional therapy. MMWR Recomm. Rep. 52, 1\u201316 (2003).","journal-title":"MMWR Recomm. Rep."},{"key":"BFsrep31003_CR21","first-page":"317","volume":"8","author":"N Hamajima","year":"2007","unstructured":"Hamajima, N. & J-MICC Study Group. The Japan Multi-Institutional Collaborative Cohort Study (J-MICC Study) to detect gene-environment interactions for cancer. Asian Pac. J. Cancer Prev. 8, 317\u2013323 (2007).","journal-title":"Asian Pac. J. Cancer Prev."},{"key":"BFsrep31003_CR22","first-page":"137","volume":"71","author":"Y Asai","year":"2009","unstructured":"Asai, Y. et al. Baseline data of Shizuoka area in the Japan Multi-Institutional Collaborative Cohort Study (J-MICC Study). Nagoya J. Med. Sci. 71, 137\u2013144 (2009).","journal-title":"Nagoya J. Med. Sci."},{"key":"BFsrep31003_CR23","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1007\/s13577-013-0081-8","volume":"27","author":"M Sakiyama","year":"2014","unstructured":"Sakiyama, M. et al. Common variant of leucine-rich repeat-containing 16A (LRRC16A) gene is associated with gout susceptibility. Hum. Cell 27, 1\u20134 (2014).","journal-title":"Hum. Cell"},{"key":"BFsrep31003_CR24","doi-asserted-by":"publisher","first-page":"490","DOI":"10.2133\/dmpk.DMPK-14-SC-041","volume":"29","author":"M Sakiyama","year":"2014","unstructured":"Sakiyama, M. et al. Ethnic differences in ATP-binding cassette transporter, sub-family G, member 2 (ABCG2\/BCRP): Genotype combinations and estimated functions. Drug Metab. Pharmacokinet. 29, 490\u2013492 (2014).","journal-title":"Drug Metab. Pharmacokinet."},{"key":"BFsrep31003_CR25","doi-asserted-by":"publisher","first-page":"3755","DOI":"10.1038\/srep03755","volume":"4","author":"H Matsuo","year":"2014","unstructured":"Matsuo, H. et al. ABCG2 dysfunction causes hyperuricemia due to both renal urate underexcretion and renal urate overload. Sci. Rep. 4, 3755 (2014).","journal-title":"Sci. Rep."},{"key":"BFsrep31003_CR26","unstructured":"R: A language and environment for statistical computing. (R. Foundation for Statistical Computing, Vienna, 2014)."},{"key":"BFsrep31003_CR27","doi-asserted-by":"publisher","first-page":"183","DOI":"10.1046\/j.1469-1809.2002.00112.x","volume":"66","author":"Y Kitamura","year":"2002","unstructured":"Kitamura, Y. et al. Determination of probability distribution of diplotype configuration (diplotype distribution) for each subject from genotypic data using the EM algorithm. Ann. Hum. Genet. 66, 183\u2013193 (2002).","journal-title":"Ann. Hum. Genet."}],"container-title":["Scientific Reports"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/srep31003.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/srep31003","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/srep31003.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,1,5]],"date-time":"2023-01-05T00:39:12Z","timestamp":1672879152000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/srep31003"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2016,8,30]]},"references-count":27,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2016,8,30]]}},"alternative-id":["BFsrep31003"],"URL":"https:\/\/doi.org\/10.1038\/srep31003","relation":{},"ISSN":["2045-2322"],"issn-type":[{"value":"2045-2322","type":"electronic"}],"subject":[],"published":{"date-parts":[[2016,8,30]]},"assertion":[{"value":"5 April 2016","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"11 July 2016","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"30 August 2016","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"Yes, there is potential competing interest: H.M., T. Takada, K.I. and N.S. have a patent pending based on the work reported in this paper. Other authors have declared that no competing interests exist.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"31003"}}