title: Genetics of hyperuricemia and gout: implications for the present and future.
abstract: 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.
authors: Division of Rheumatology and Immunology, Duke University School of Medicine, DUMC, NC 27710, USA.
authors: Ronald L
authors: RL
authors: George
authors: Robert T
authors: RT
authors: Keenan
mesh_terms: D000070997:ATP Binding Cassette Transporter, Subfamily G, Member 2; D018528:ATP-Binding Cassette Transporters / Q000235:genetics; D005544:Forecasting; D051246:Glucose Transport Proteins, Facilitative / Q000235:genetics; D006073:Gout / Q000150:complications / Q000188:drug therapy / Q000235:genetics*; D006074:Gout Suppressants / Q000009:adverse effects / Q000627:therapeutic use; D006801:Humans; D033461:Hyperuricemia / Q000150:complications / Q000188:drug therapy / Q000235:genetics*; D009363:Neoplasm Proteins / Q000235:genetics; D027361:Organic Anion Transporters / Q000235:genetics; D027701:Organic Cation Transport Proteins / Q000235:genetics
chemical_list: C116614:ABCG2 protein, human; D000070997:ATP Binding Cassette Transporter, Subfamily G, Member 2; D018528:ATP-Binding Cassette Transporters; D051246:Glucose Transport Proteins, Facilitative; D006074:Gout Suppressants; D009363:Neoplasm Proteins; D027361:Organic Anion Transporters; D027701:Organic Cation Transport Proteins; C491241:SLC22A12 protein, human; C411811:SLC2A9 protein, human