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What lies behind serum urate concentration? Insights from genetic and genomic studies

DOI: 10.1186/gm118

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Abstract:

Hyperuricemia induces or facilitates gout, kidney stones, metabolic syndrome, hypertension and renal and cardiovascular disease, while exercise-induced acute renal failure is a significant complication of renal hypouricemia [1-3]. Although hyperuricemia has been more closely associated with gout and kidney stones, it has been recently recognized to be independently associated with components of metabolic syndrome, insulin resistance, hypertension, dyslipidemia and obesity. Metabolic syndrome is a clustering of cardiovascular disease risk factors and its prevalence is increasing. Several mechanisms for the association between hyperuricemia and metabolic syndrome have been proposed; insulin resistance leads to renal underexcretion of uric acid (urate); increased lactate in obesity accelerates renal urate reabsorption via urate transporter 1 (URAT1); fatty acid synthesis accelerates de novo purine synthesis via the pentose phosphate pathway, and so on [4]. Recent studies have shown that hyperuricemia independently causes atherosclerosis through urate-mediated inflammation and endothelial dysfunction, in addition to metabolic syndrome [5,6]. Thus, monitoring of serum urate concentrations in patients with hyperuricemia, kidney stones, metabolic syndrome, or renal or cardiovascular disease has been recommended, at least after a certain age.Urate is the end product of human purine metabolism and is mainly excreted in urine. Serum urate concentrations are determined by the volume of urate produced via purine metabolism and by renal urate excretion. Many factors, including genetic components and acquired factors such as obesity and alcohol consumption, influence serum urate concentrations. Genetic links to serum urate concentrations have been identified, mainly from earlier studies of monogenic disorders, but have also been recently analyzed using genome-wide association approaches. Monogenic disorders such as hypoxanthine-guanine phosphoribosyl transferase deficiency (Lesch

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