SLC2A9 is a newly identified urate transporter influencing serum urate concentration, urate excretion and gout. | Read by QxMD

Veronique Vitart, Igor Rudan, Caroline Hayward, Nicola K Gray, James Floyd, Colin N A Palmer, Sara A Knott, Ivana Kolcic, Ozren Polasek, Juergen Graessler, James F Wilson, Anthony Marinaki, Philip L Riches, Xinhua Shu, Branka Janicijevic, Nina Smolej-Narancic, Barbara Gorgoni, Joanne Morgan, Susan Campbell, Zrinka Biloglav, Lovorka Barac-Lauc, Marijana Pericic, Irena Martinovic Klaric, Lina Zgaga, Tatjana Skaric-Juric, Sarah H Wild, William A Richardson, Peter Hohenstein, Charley H Kimber, Albert Tenesa, Louise A Donnelly, Lynette D Fairbanks, Martin Aringer, Paul M McKeigue, Stuart H Ralston, Andrew D Morris, Pavao Rudan, Nicholas D Hastie, Harry Campbell, Alan F Wright

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 microM) compared with other mammals (3-120 microM). 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.