Dehghan A et al. (2008) Association of three genetic loci with uric acid concentration and risk of gout: a genome-wide association study. Lancet [doi:10.1016/s0140-6736(08)61343-4]

Via the use of genome-wide association studies, Dehghan et al. have confirmed a previously identified association between genetic variation in SLC2A9 and both serum uric acid concentration and risk of gout in white individuals. In addition, they demonstrated that this same association was present in black people, and identified two new candidate loci (in ABCG2 and SLC17A2) that show similar associations.

The initial genome-wide screen looked for gene variants that correlated significantly with levels of uric acid in participants from the Framingham and Rotterdam cohorts. Five candidate single-nucleotide polymorphisms were identified, clustered within three genetic loci. The Atherosclerosis Risk in Communities (ARIC) study genotyped three of these polymorphisms and found associations between them (one per locus) and both serum uric acid concentration and risk of gout. All three loci are thought to influence renal urate transportation. The number of risk alleles harbored by individuals in all three cohorts showed strong, linear correlations with serum uric acid concentrations and with prevalence gout. Across all three cohorts, the prevalence of gout in individuals without risk alleles was 1–2%, which rose to 8–18% in those with six risk alleles.

The number of risk alleles present in an individual could potentially be developed as a screening tool to predict the risk of gout in asymptomatic individuals, to decide whether asymptomatic hyperuricemia should be treated, and to ensure that individuals with a putative genetic predisposition to gout do not receive treatments contraindicated in that condition.