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The M\u0101ori and Pacific (Polynesian) population of New Zealand has the highest prevalence of gout worldwide. The aim of this study was to determine whether any Polynesian population\u2013specific genetic variants in <jats:italic>SLC22A6\u20138<\/jats:italic> and <jats:italic>ABCC4<\/jats:italic> are associated with gout.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>All participants had \u22653 self\u2010reported M\u0101ori and\/or Pacific grandparents. Among the total sample set of 1,808 participants, 191 hyperuricemic and 202 normouricemic individuals were resequenced over the 4 genes, and the remaining 1,415 individuals were used for replication. Regression analyses were performed, adjusting for age, sex, and Polynesian ancestry. To study the functional effect of nonsynonymous variants of <jats:italic>ABCC4<\/jats:italic>, transport assays were performed in <jats:italic>Xenopus laevis<\/jats:italic> oocytes.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>A total of 39 common variants were detected, with an <jats:italic>ABCC4<\/jats:italic> variant (rs4148500) significantly associated with hyperuricemia and gout. This variant was monomorphic for the urate\u2010lowering allele in Europeans. There was evidence for an association of rs4148500 with gout in the resequenced samples (odds ratio [OR] 1.62 [<jats:italic>P<\/jats:italic>\u2009=\u20090.012]) that was replicated (OR 1.25 [<jats:italic>P<\/jats:italic>\u2009=\u20090.033]) and restricted to men (OR 1.43 [<jats:italic>P<\/jats:italic>\u2009=\u20090.001] versus OR 0.98 [<jats:italic>P<\/jats:italic>\u2009=\u20090.89] in women). The gout risk allele was associated with fractional excretion of uric acid in male individuals (\u03b2\u2009=\u2009\u22120.570 [<jats:italic>P<\/jats:italic>\u2009=\u20090.01]). A rare population\u2010specific allele (P1036L) with predicted strong functional consequence reduced the uric acid transport activity of <jats:italic>ABCC4<\/jats:italic> by 30%.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>An association between <jats:italic>ABCC4<\/jats:italic> and gout and fractional excretion of uric acid is consistent with the established role of MRP4 as a unidirectional renal uric acid efflux pump.<\/jats:p><\/jats:sec>","DOI":"10.1002\/art.40110","type":"journal-article","created":{"date-parts":[[2017,3,28]],"date-time":"2017-03-28T15:58:29Z","timestamp":1490716709000},"page":"1461-1469","source":"Crossref","is-referenced-by-count":58,"title":["Population\u2010Specific Resequencing Associates the ATP\u2010Binding Cassette Subfamily C Member 4 Gene With Gout in New Zealand M\u0101ori and Pacific Men"],"prefix":"10.1002","volume":"69","author":[{"given":"Callum","family":"Tanner","sequence":"first","affiliation":[{"name":"University 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Otago Dunedin New Zealand"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amanda J.","family":"Phipps\u2010Green","sequence":"additional","affiliation":[{"name":"University of Otago Dunedin New Zealand"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ruth K.","family":"Topless","sequence":"additional","affiliation":[{"name":"University of Otago Dunedin New Zealand"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jennie Harr\u00e9","family":"Hindmarsh","sequence":"additional","affiliation":[{"name":"Ngati Porou Hauora Charitable Trust Te Puia Springs New Zealand"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lisa K.","family":"Stamp","sequence":"additional","affiliation":[{"name":"University of Otago Christchurch Christchurch New Zealand"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicola","family":"Dalbeth","sequence":"additional","affiliation":[{"name":"University of Auckland Auckland New Zealand"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hyon K.","family":"Choi","sequence":"additional","affiliation":[{"name":"Massachusetts General Hospital, Harvard Medical School Boston"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David B.","family":"Mount","sequence":"additional","affiliation":[{"name":"Brigham and Women's Hospital and VA Boston Healthcare System, Harvard Medical School Boston Massachusetts"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tony R.","family":"Merriman","sequence":"additional","affiliation":[{"name":"University of Otago Dunedin New 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