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Title: Three Genes, Risk Score Can Facilitate Risk Prediction of Gout
URL: http://www.pslgroup.com/dg/22DF9A.htm
Doctor's Guide
October 1, 2008

NEW YORK -- October 1, 2008 -- Researchers have shown that 3 genes are associated with increased risk of gout, according to a study published early online and in an upcoming edition of The Lancet.

According to the authors, a genetic risk score based on these genes could reveal those at highest risk of the condition long before onset of clinical symptoms and facilitate early, targeted, and/or new treatments.

Caroline Fox, MD, National Heart Lung and Blood Institute, Bethesda, Maryland, and colleagues used data from participants in 2 cohorts: 7,699 from the Framingham Heart Study and 4,148 from the Rotterdam Study.

Both cohorts were genetically analysed to determine which genes were associated with serum uric acid, and the results were further replicated in both white (n = 11,024) and black (n = 3,843) participants in the Atherosclerosis Risk in Communities (ARIC) study.

The research confirmed the association of the gene SLC2A9 with gout and also revealed 2 more genes, ABCG2 and SLC17A3, which are likely to be kidney urate transporters. An additive genetic risk score of these high-risk alleles showed graded associations with uric acid levels in all 3 cohorts.

Gout prevalence was found to be 2% to 13% in the Framingham cohort, 2% to 8% in the Rotterdam cohort, and 1% to 18% in white participants in the ARIC study.

"Our genetic risk score was associated with up to 40-fold increased risk of developing gout, which is substantially higher than that for environmental risk factors, suggesting that knowledge of genotype could help to identify individuals at risk of developing gout long before onset of clinical features of the disease. This result underscores the value of a single assessment of the genetic risk score, whereas the measurement of uric acid concentration depends on measurement error and physiological variation over time," the authors write.

"In addition to risk prediction, knowledge of an individual's genotype or risk score could be used to help guide clinical decisions, especially with respect to selection of drugs that are known to increase uric acid concentration and worsen gout. At present, prophylaxis for asymptomatic hyperuricaemia is not recommended, but our genetic risk score could be used to identify individuals in which asymptomatic hyperuricaemia should be treated. ... The genes identified in our study could be useful for the ascertainment of novel proteins and molecular mechanisms that affect uric acid concentration and for novel drug targets to improve treatment of gout."


SOURCE: The Lancet

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