SLC2A9 is a newly identified urate transporter influencing serum urate concentration, urate excretion and gout

• Published in: Nature genetics Vol. 40; no. 4; pp. 437 - 442
• Main Authors: Wright, Alan F, Vitart, Veronique, Rudan, Igor, Hayward, Caroline, Gray, Nicola K, Floyd, James, Palmer, Colin NA, Knott, Sara A, Kolcic, Ivana, Polasek, Ozren, Graessler, Juergen, Wilson, James F, Marinaki, Anthony, Riches, Philip L, Shu, Xinhua, Janicijevic, Branka, Smolej-Narancic, Nina, Gorgoni, Barbara, Morgan, Joanne, Campbell, Susan, Biloglav, Zrinka, Barac-Lauc, Lovorka, Pericic, Marijana, Klaric, Irena Martinovic, Zgaga, Lina, Skaric-Juric, Tatjana, Wild, Sarah H, Richardson, William A, Hohenstein, Peter, Kimber, Charley H, Tenesa, Albert, Donnelly, Louise A, Fairbanks, Lynette D, Aringer, Martin, McKeigue, Paul M, Ralston, Stuart H, Morris, Andrew D, Rudan, Pavao, Hastie, Nicholas D, Campbell, Harry
• Format: Journal Article
• Language: English
• Published: New York Nature Publishing Group US 01.04.2008; Nature Publishing Group
• Subjects: Acids; Adolescent; Adult; Aged; Aged, 80 and over; Agriculture; Animal Genetics and Genomics; Animals; Biological and medical sciences; Biological Transport, Active; Biomarkers - blood; Biomarkers - urine; Biomedical and Life Sciences; Biomedicine; Cancer Research; Care and treatment; Case-Control Studies; Complications and side effects; Croatia; Crystals; Diagnosis; Diseases of the osteoarticular system; Excretion; Female; Fructose - metabolism; Fundamental and applied biological sciences. Psychology; Gene Function; Genetic Linkage; Genetic variance; Genetics of eukaryotes. Biological and molecular evolution; Genome, Human; Genomics; Genotype; Germany; Glucose Transport Proteins, Facilitative - physiology; Gout; Gout - blood; Gout - urine; Health aspects; Human Genetics; Human populations; Humans; Hyperuricemia; Inflammatory joint diseases; Kidneys; letter; Male; Mammals; Medical sciences; Middle Aged; Miscellaneous. Osteoarticular involvement in other diseases; Molecular Sequence Data; Oocytes - cytology; Oocytes - metabolism; Organic Anion Transporters - metabolism; Polymorphism, Single Nucleotide - genetics; Population genetics; Rheumatism; Risk factors; Uric acid; Uric Acid - blood; Urinary tract diseases; Xenopus laevis; Xenopus laevis - metabolism; Germany; Croatia; British Isles; Hyperuricemia; Excretion; Gout; Diseases of the osteoarticular system; Metabolic diseases; Serum; Purine; Uric acid; Concentration; Microcristalline arthropathy; Microcrystal
• ISSN: 1061-4036; 1546-1718
• DOI: 10.1038/ng.106

Uric acid is the end product of purine metabolism in humans and great apes, which have lost hepatic uricase activity, leading to uniquely high serum uric acid concentrations (200-500 μM) compared with other mammals (3-120 μM). About 70% of daily urate disposal occurs via the kidneys, and in 5-25% of the human population, impaired renal excretion leads to hyperuricemia. About 10% of people with hyperuricemia develop gout, an inflammatory arthritis that results from deposition of monosodium urate crystals in the joint. We have identified genetic variants within a transporter gene, SLC2A9, that explain 1.7-5.3% of the variance in serum uric acid concentrations, following a genome-wide association scan in a Croatian population sample. SLC2A9 variants were also associated with low fractional excretion of uric acid and/or gout in UK, Croatian and German population samples. SLC2A9 is a known fructose transporter, and we now show that it has strong uric acid transport activity in Xenopus laevis oocytes.