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)1. About 70% of daily urate disposal occurs via the kidneys, and in 5–25% of the human population, impaired renal excretion leads to hyperuricemia2. 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 transporter3, and we now show that it has strong uric acid transport activity in Xenopus laevis oocytes.
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This research was funded by grants from the Medical Research Council (UK), the Wellcome Trust, Arthritis Research Campaign (S.H.R.), and Cancer Research UK (A.T.), an MRC Senior Non-Clinical Fellowship (N.K.G.), and Republic of Croatia Ministry of Science, Education and Sports grants to I.R. (108-1080315-0302), P.R. (196-1962766-2751), B.J. (196-1962766-2763) and N.S.-N. (196-1962766-2747). The Croatian and Scottish (Orcadian) groups are now components of the EU Framework 6 project EUROSPAN (Contract No. LSHG-CT-2006-018947) (I.R., H.C., J.F.W., A.F.W., N.D.H.). We thank G.W. Gould, C.I. Cheeseman and I. White for helpful discussions and advice. We acknowledge the Wellcome Trust Clinical Research Facility (Edinburgh) for performing DNA extractions (Orkney) and the genome-wide association scan, J. Ireland for computing support and C. Nicol for the figures. Special thanks to K. Wilson and R. Bisset for administrative support.
We have filed a patent application based on this work.
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Vitart, V., Rudan, I., Hayward, C. et al. SLC2A9 is a newly identified urate transporter influencing serum urate concentration, urate excretion and gout. Nat Genet 40, 437–442 (2008). https://doi.org/10.1038/ng.106
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