Grant: Operating Grant

Humans have very high circulating levels of urate in their blood compared to other mammals. The physiological reason for this is not known, however even small additional increases in this concentration is associated with several metabolic diseases including gout and diabetes. The normal regulation of urate in the blood is controlled primarily by the kidney through several proteins which can either reabsorb urate from the urine or secrete it back into the urine. We have recently discovered a new protein which can transport urate in the kidney and we proposed that this protein may be a key player in secreting urate into the urine, i.e. lowering plasma urate concentrations. Further, a genetic screen indicates that a series of polymorphisms (slight genetic variations) within the gene coding for this protein may be related both to the incidence of gout and/ or hypertension in some populations. This project contains experiments designed to test just how this protein moves urate out of (or into) different cell types and in particular tests our hypothesis that it plays a key role in the kidney. If our hypothesis proves to be correct this may identify a new drug target for the treatment of gout and hypertension