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Potential Target for Gout Treatment Is Identified

Researchers at Johns Hopkins and the University of Texas-Houston have shown that a gene, located in a chromosome 4 region statistically associated with gout, is functionally associated with the disease. The gene is ABCG2 (ATP-binding cassette, subfamily G, 2) and the researchers showed that it is a previously unidentified urate efflux transporter. The researchers further showed that the native ABCG2 protein is located in the brush border membrane of proximal kidney tubule cells where it mediates renal urate secretion. Introduction of a common SNP mutation into the gene resulted in 53% reduced urate transport rates in an experimental model. Data from a population-based study supports the fact that this particular SNP is a causal variant in the gout-associated region on chromosome 4. The authors also said that their data indicates that this common casual variant is responsible for at least 10 percent of all gout cases in whites. Noting that gout affects approximately 3 million people in the United States and that present treatments are often insufficient, the researchers suggested that ABCG2 represents an attractive drug target. This work was published online on June 8 in PNAS. Gout is a disease hallmarked by elevated levels of uric acid in the bloodstream. In this condition, crystals of monosodium urate, a uric acid salt, are deposited on the articular cartilage of joints, tendons, and surrounding tissues. The disease is marked by transient painful attacks of acute arthritis initiated by crystallization of urates within and about the joints, and can eventually lead to chronic gouty arthritis and the deposition of masses of urates in joints and other sites. [PNAS abstract]