{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T19:24:26Z","timestamp":1791919466181,"version":"4.3.4"},"reference-count":38,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2019,5,23]],"date-time":"2019-05-23T00:00:00Z","timestamp":1558569600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100008069","name":"University of California, San Francisco","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100008069","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R01DK103729"],"award-info":[{"award-number":["R01DK103729"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["ascpt.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Clin Pharma and Therapeutics"],"published-print":{"date-parts":[[2019,9]]},"abstract":"<jats:p>Allopurinol, which lowers uric acid (<jats:styled-content style=\"fixed-case\">UA<\/jats:styled-content>) concentration, is increasingly being recognized for its benefits in cardiovascular and renal disease. However, response to allopurinol is variable. We gathered samples from 4,446 multiethnic subjects for a genome\u2010wide association study of allopurinol response. Consistent with previous studies, we observed that the Q141K variant in <jats:italic><jats:styled-content style=\"fixed-case\">ABCG<\/jats:styled-content>2<\/jats:italic> (rs2231142), which encodes the efflux pump breast cancer resistance protein (<jats:styled-content style=\"fixed-case\">BCRP<\/jats:styled-content>), associated with worse response to allopurinol. However, for the first time this association reached genome\u2010wide level significance (<jats:italic>P\u00a0<\/jats:italic>=\u00a08.06\u00a0\u00d7\u00a010<jats:sup>\u221211<\/jats:sup>). Additionally, we identified a novel association with a variant in <jats:italic><jats:styled-content style=\"fixed-case\">GREM<\/jats:styled-content>2<\/jats:italic> (rs1934341, <jats:italic>P\u00a0<\/jats:italic>=\u00a03.22\u00a0\u00d7\u00a010<jats:sup>\u22126<\/jats:sup>). <jats:italic>In vitro<\/jats:italic> studies identified oxypurinol, the active metabolite of allopurinol, as an inhibitor of the <jats:styled-content style=\"fixed-case\">UA<\/jats:styled-content> transporter <jats:styled-content style=\"fixed-case\">GLUT<\/jats:styled-content>9, suggesting that oxypurinol may modulate <jats:styled-content style=\"fixed-case\">UA<\/jats:styled-content> reabsorption. These results provide strong evidence for a role of <jats:styled-content style=\"fixed-case\">BCRP<\/jats:styled-content> Q141K in allopurinol response, and suggest that allopurinol may have additional hypouricemic effects beyond xanthine oxidase inhibition.<\/jats:p>","DOI":"10.1002\/cpt.1439","type":"journal-article","created":{"date-parts":[[2019,3,29]],"date-time":"2019-03-29T04:23:28Z","timestamp":1553833408000},"page":"623-631","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":33,"title":["Genome\u2010Wide Association and Functional Studies Reveal Novel Pharmacological Mechanisms for Allopurinol"],"prefix":"10.1111","volume":"106","author":[{"given":"Deanna J.","family":"Brackman","sequence":"first","affiliation":[{"name":"Department of Bioengineering and Therapeutic Sciences University of California San Francisco  San Francisco California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sook Wah","family":"Yee","sequence":"additional","affiliation":[{"name":"Department of Bioengineering and Therapeutic Sciences University of California San Francisco  San Francisco California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Osatohanmwen J.","family":"Enogieru","sequence":"additional","affiliation":[{"name":"Department of Bioengineering and Therapeutic Sciences University of California San Francisco  San Francisco California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christian","family":"Shaffer","sequence":"additional","affiliation":[{"name":"Department of Biomedical Informatics Vanderbilt University Medical Center  Nashville Tennessee USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dilrini","family":"Ranatunga","sequence":"additional","affiliation":[{"name":"Kaiser Permanente Northern California Division of Research  Oakland California 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