Genetics of Hyperuricemia and Gout: Implications for the Present and Future
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Gout is the most common inflammatory arthropathy and occurs in the setting of elevated serum urate levels. Gout is also known to be associated with multiple comorbidities including cardiovascular disease and the metabolic syndrome. Recent advances in research have increased our understanding and improved our knowledge of the pathophysiology of gout. Genome-wide association studies have permitted the identification of several new and common genetic factors that contribute to hyperuricemia and gout. Most of these are involved with the renal urate transport system (the uric acid transportasome), generally considered the most influential regulator of serum urate homeostasis. Thus far, SCL22A12, SCL2A9, and GLUT9 have been found to have the greatest variation and most influence on serum urate levels. However, genetics are only a part of the explanation in the development of hyperuricemia and gout. As results have been mixed, the role of known urate influential genes in gout’s associated comorbidities remains unclear. Regardless, GWAS findings have expanded our understanding of the pathophysiology of hyperuricemia and gout, and will likely play a role in the development of future therapies and treatment of this ancient disease.
KeywordsGout Genetics Hyperuricemia Urate transporters Crystal arthritis Therapy Renal urate homeostasis Management Medication safety
Dr. Keenan has served as a consultant for Savient and Novartis; has received grant support from Novartis; and has received payment for development of educational presentations (including service on speakers’ bureaus) from Savient, Novartis, Amgen, Abbott Laboratories, and Genentech.
Dr. George reported no potential conflicts of interest relevant to this article.
Papers of particular interest, published recently, have been highlighted as: • Of importance •• Of major importance
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