The GLUT9 Gene Is Associated with Serum Uric Acid Levels in Sardinia and Chianti Cohorts

Siguang Li(National Institute on Aging), Serena Sanna(Institute of Genetic and Biomedical Research), Andrea Maschio(Institute of Genetic and Biomedical Research), Fabio Busonero(Institute of Genetic and Biomedical Research), Gianluca Usala(Institute of Genetic and Biomedical Research), Antonella Mulas(Institute of Genetic and Biomedical Research), Sandra Lai(Institute of Genetic and Biomedical Research), Mariano Dei(Institute of Genetic and Biomedical Research), Marco Orrù(Institute of Genetic and Biomedical Research), Giuseppe Albai(Institute of Genetic and Biomedical Research), Stefania Bandinelli(Azienda Sanitaria di Firenze), David Schlessinger(National Institute on Aging), Edward G. Lakatta(National Institute on Aging), Angelo Scuteri(National Institute on Aging), Samer S. Najjar(National Institute on Aging), Jack M. Guralnik(National Institute on Aging), Silvia Naitza(Institute of Genetic and Biomedical Research), Laura Crisponi(Institute of Genetic and Biomedical Research), Antonio Cao(Institute of Genetic and Biomedical Research), Gonçalo R. Abecasis(Michigan United), Luigi Ferrucci(National Institute on Aging), Manuela Uda(Institute of Genetic and Biomedical Research), Wei-Min Chen(Michigan United), Ramaiah Nagaraja(National Institute on Aging)
PLoS Genetics
November 5, 2007
10.1371/journal.pgen.0030194
Cited by 317Open Access
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Abstract

High serum uric acid levels elevate pro-inflammatory-state 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 x 10(-16)), along with eight others (p = 7.75 x 10(-16) to 6.05 x 10(-11)). 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.

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