Urate transporters in the genomic era
- 1 September 2013
- journal article
- review article
- Published by Ovid Technologies (Wolters Kluwer Health) in Current Opinion in Nephrology and Hypertension
- Vol. 22 (5), 545-550
- https://doi.org/10.1097/mnh.0b013e328363ffc8
Abstract
Recent advances in genome technology have provided us with a list of molecules affecting urate handling in humans, many of which are unlikely to be identified through traditional physiological approach alone. Although this article is focused on urate, this can be viewed as a successful model of genomics-physiology collaboration. URATv1/GLUT9 (SLC2A9) is shown to play a critical role in urate reabsorption at the proximal tubule, probably more prominent than its partner URAT1 (SLC22A12). The major site of action of ABCG2 (ABCG2), an influential urate secretion transporter, has been shown to be the intestine rather than the kidney proximal tubule. Accordingly, hypofunction of ABCG2 leads to increased fractional excretion of urate, a finding traditionally interpreted as overproduction hyperuricemia. Some SLC17 family members secrete urate in the kidney or intestine. OAT2 (SLC22A7) may take up urate from blood to the proximal tubular cell. In addition, how a common single-nucleotide polymorphisms in ABCG2 affects its function has been elucidated. A finer grained picture of urate handling in the human body is now emerging, which will help choosing novel targets for urate-lowering therapy.Keywords
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