Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0018099 (gout)
 5,192 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Uric acid is the end product of purine metabolism in humans and great apes, which have lost hepatic uricase activity, leading to uniquely high serum uric acid concentrations (200-500 microM) compared with other mammals (3-120 microM). About 70% of daily urate disposal occurs via the kidneys, and in 5-25% of the human population, impaired renal excretion leads to hyperuricemia. About 10% of people with hyperuricemia develop gout, an inflammatory arthritis that results from deposition of monosodium urate crystals in the joint. We have identified genetic variants within a transporter gene, SLC2A9, that explain 1.7-5.3% of the variance in serum uric acid concentrations, following a genome-wide association scan in a Croatian population sample. SLC2A9 variants were also associated with low fractional excretion of uric acid and/or gout in UK, Croatian and German population samples. SLC2A9 is a known fructose transporter, and we now show that it has strong uric acid transport activity in Xenopus laevis oocytes.
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PMID:SLC2A9 is a newly identified urate transporter influencing serum urate concentration, urate excretion and gout. 1832 57

Genetic variation in the SLC2A9 gene is a new genetic risk factor for low fractional excretion of uric acid, hyperuricemia, and gout. Its gene product, GLUT9, was previously known as a type II glucose/fructose transporter but is now known to function as a high-capacity uric acid transporter that is expressed in kidney, liver, and several other tissues. Follow-up meta-analyses, including one with data from 28,141 individuals, implicated a total of nine additional loci influencing serum urate concentrations, including six other membrane transporters (SLC17A1, SLC17A3, SLC22A11, SLC22A12, SLC16A9, and ABCG2). Variants in these genes together account for about 5% of the variance in serum urate, two-thirds of which is due to SLC2A9. Using these variants in 'Mendelian randomization' analyses provides a powerful means of dissecting the role of urate in cardiovascular and metabolic diseases, where cause-and-effect influences are difficult to discern due to potential confounding. The results highlight the complex interplay of membrane transporters involved in urate metabolism. They also show how variants of weak effect identified by genome-wide association studies can still be important in identifying novel pathways, including a 'complexity' of new and potentially druggable targets for modifying urate transport.
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PMID:A 'complexity' of urate transporters. 2061 16