Genetic and Environmental Risk Factors in Hyperuricaemia and Common Gout

Author(s): Tony R. Merriman, Nicola Dalbeth

Journal Name: Current Rheumatology Reviews

Volume 7 , Issue 2 , 2011

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Gout results from hyperuricaemia. The most important cause of hyperuricaemia is reduced excretion of uric acid in the urine. Genome-wide association scans for genes regulating serum urate concentrations have identified two major regulators – the renal urate transporters SLC2A9 and ABCG2. The risk variants at each gene approximately double the risk for gout in people of Caucasian ancestry, with the urate and fructose transporter SLC2A9 also resulting in higher risk for gout in people of Polynesian ancestry, a diverse population characterized by a high prevalence of gout. Ongoing genetic association studies are identifying and confirming other genes (URAT1, OAT4, NPT1, PDZK1, GCKR) controlling serum urate concentrations; although genome-wide association studies in gout per se await recruitment of suitable case sample sets. The recent increase in gout incidence can only be explained by a change in the environment. One factor that fulfills most of the requirements for confirmation of an etiological role in gout is fructose. Fructose raises serum urate levels, which is exacerbated in people with genetic variants that reduce renal urate excretion, thus increasing the risk of gout. Use of GWAS approaches and application of new genomics technologies such as next-generation sequencing to very large well-phenotyped gout sample sets will enable identification of further genetic risk factors in gout. Intervention studies in cohorts characterized for genetic risk factors are needed to prove a direct link for environmental agents such as fructose in gout etiology.

Keywords: Gout, gene, urate transporter, association, genome, SLC2A9, monosodium urate, Caucasian, Hyperuricaemia, polymorphisms, glucokinase

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Article Details

Year: 2011
Page: [114 - 122]
Pages: 9
DOI: 10.2174/157339711795305013
Price: $65

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