Researchers have identified two new genes – and confirmed the role of a third gene – associated with increased risk of higher levels of uric acid in the blood, which can lead to gout, a common, painful form of arthritis. Combined, the three genetic variations were associated with up to a 40-fold increased risk in developing gout. The findings suggest that genetic testing could one day be used to identify individuals at risk for gout before symptoms develop, as well as determine who might benefit from medications to prevent the development of gout.
The study was supported by the National Heart, Lung, and Blood Institute (NHLBI) of the National Institutes of Health (NIH) and the Netherlands organization for scientific research (NWO). Additional support from the NIH's National Center for Research Resources and through the NIH Roadmap for Medical Research was provided.
"We identified two novel loci [genes] for uric acid that were also associated with gout," said lead researcher Dr. Caroline Fox, from the NHLBI. These genes, "can potentially be used as novel drug targets" against the disease, she said.
The genes were identified using data from two large genome-wide association studies – genetic variations of nearly 7,700 participants from NHLBI's Framingham Heart Study SHARe (SNP Health Association Resource) and more than 4,100 participants in NWO's Rotterdam Study. Researchers then replicated their finding using data from nearly 14,900 participants in NHLBI's Atherosclerosis Risk in Communities Study (ARIC).
Fox's group found an association with the gene involved in urate transport in the kidney-- the SCLA29 gene, as well as two genes which are likely to be involved in urate transport-- the ABCG2 and SLC17A3 genes.
Among people in the Framingham study, 2 percent to 13 percent had gout, as did 2 percent to 8 percent of those in the Rotterdam study and 1 percent to 18 percent of whites enrolled in the Atherosclerosis study, the researchers found.
The additive effect of having all three gene variants can increase the risk for gout 40-fold, the researchers reported. This increased risk is substantially higher than other factors that account for developing the disease.
"Small effects from multiple genes can be associated with substantial risk for disease," Fox noted.
Nearly 3 million adults in the United States are estimated to have gout. Gout can develop when excess amounts of uric acid build up in the blood and form crystals, which accumulate in the joints causing swelling and pain. Left untreated over time, gout can permanently damage affected joints and, possibly, the kidneys.
Illustration: Microsoft clipart.
National Heart, Lung, & Blood Institute News Release (09/30/08)
Washington Post (09/30/08)
Abstract (The Lancet; (10/01/08))