Three Genes Raise Gout Risk
TUESDAY Sept. 30, 2008 -- Three genes may raise risks for painful gout by up to 40 times, researchers report.
The finding could help identify people at risk for the arthritic illness, long before symptoms start. One of the genes studied had already been associated with gout, but identifying all three genes could help develop new treatments.
Gout is a very painful form of arthritis caused by a buildup of uric acid. This causes uric acid crystals to be deposited on the cartilage of joints, tendons and other surrounding tissue, especially in the feet, causing an inflammatory reaction.
"We identified two novel loci [genes] for uric acid that were also associated with gout," said lead researcher Dr. Caroline Fox, from the U.S. National Heart, Lung, and Blood Institute. These genes, "can potentially be used as novel drug targets" against the disease, she said.
The report was published in the Sept. 30 online edition of The Lancet.
For the study, Fox's team looked at the genetic makeup of almost 7,700 people who participated in the Framingham Heart Study and more than 4,100 people from the Rotterdam Study. They found three genes associated with uric acid, a biomarker for gout.
To confirm their findings, Fox's group replicated their study in more than 11,000 whites and 3,800 blacks who took part in the Atherosclerosis Risk in Communities study.
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.
Dr. Martin Aringer, from the Division of Rheumatology at the University Clinical Centre Carl Gustav Carus in Dresden, Germany, and author of an accompanying journal editorial, believes the findings could have an impact on treating gout.
"The main problem in gout is a problem in renal excretion," Aringer explained. "More than 90 percent of all gout patients are not able to get rid of uric acid the way they should," he said.
"All these polymorphism [gene types] are pretty common. If you have several polymorphisms, then you are very likely to get gout," he said.
By understanding the genetic components that increase the risk for gout, it might be possible to develop new medications that could target the disease more directly, Aringer said.
In addition, some of these genes could play a role in diabetes and other diseases, Aringer said. "New medications might change things we can't even speculate about today," he said.
For more about gout, visit the U.S. National Library of Medicine.
Posted: September 2008
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