Probable Potential Role of Urate Transporter Genes in the Development of Metabolic Disorders

摘要

Metabolic disorders are a group of interrelated conditions which increases the risk of developing heart diseases, stroke, and diabetes. These usually occur as a consequence of deficiency of enzymes involved in biochemical reactions in the body. The dietary habits, lack of physical exercise, stress, and genetic susceptibility leads to an increased risk of developing metabolic disorders. A diet rich in processed food items containing high calories aggravates the production of a purine metabolite, the uric acid (UA). UA functions as an antioxidant, protects against inflammation, aging, and cancer. It exists as urate ions in the circulation and blood level of UA is maintained by a balance between its production in the liver and its excretion by the renal tubules. The regular excretion of UA through the kidneys is necessary to maintain optimum blood levels of UA (3-7 mg/dl). There are various transporters of uric acid present around the renal tubules, which help in reabsorption of UA into the blood. These urate transporters (UT) are proteins coded in the genes. Mutations in these genes may prompt disturbances in UA reabsorption, and could lead to the development of hyperuricaemia, insulin resistance, endothelial dysfunction, diabetes and other metabolic diseases. This paper reviews eight such genes coding for UTs and attempts to unravel the link between the activities of UA, UTs, and the consequences during mutations in the genes coding for the UTs in the development of metabolic disorders. The genes reviewed included SLC2A9, SLC17A1, SLC22A12, SLC16A9, GCKR, LRRC16A, PDZK1, and ABCG2.