High serum uric acid levels elevate pro-inflammatorystate gout crystal arthropathy and place individuals at high risk for
cardiovascular morbidity and mortality. Genome-wide scans in the genetically isolated Sardinian population identified variants associated with serum uric acid levels as a quantitative trait. They mapped within GLUT9, a Chromosome 4 glucose transporter gene predominantly expressed in liver and kidney. SNP rs6855911 showed the strongest association (p 1.84 1016), along with eight others (p 7.75 1016 to 6.05 1011). Individuals
homozygous for the rare
allele of rs6855911 (minor allele frequency 0.26) had 0.6 mg/dl less uric acid than those homozygous for the common allele; the results were replicated in an unrelated cohort from Tuscany. Our results suggest that polymorphisms in GLUT9 could affect glucose metabolism and uric acid synthesis and/or renal reabsorption, influencing serum uric acid levels over a wide range of values.