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

• Published in: PLoS genetics Vol. 3; no. 11; p. e194
• Main Authors: Li, Siguang, Sanna, Serena, Maschio, Andrea, Busonero, Fabio, Usala, Gianluca, Mulas, Antonella, Lai, Sandra, Dei, Mariano, Orrù, Marco, Albai, Giuseppe, Bandinelli, Stefania, Schlessinger, David, Lakatta, Edward, Scuteri, Angelo, Najjar, Samer S, Guralnik, Jack, Naitza, Silvia, Crisponi, Laura, Cao, Antonio, Abecasis, Gonçalo, Ferrucci, Luigi, Uda, Manuela, Chen, Wei-Min, Nagaraja, Ramaiah
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 01.11.2007; Public Library of Science (PLoS)
• Subjects: Adolescent; Adult; Aged; Aged, 80 and over; Cohort Studies; Colleges & universities; Deoxyribonucleic acid; Diet; DNA; Female; Genes; Genetic testing; Genetics and Genomics; Genome, Human - genetics; Genomes; Genotype; Glucose; Glucose Transport Proteins, Facilitative - genetics; Homo (Human); Humans; Italy; Linkage Disequilibrium; Male; Middle Aged; Molecular Sequence Data; Mortality; Polymorphism, Single Nucleotide - genetics; Population; Proteins; Uric Acid - blood; Italy
• ISSN: 1553-7404; 1553-7390; 1553-7404
• DOI: 10.1371/journal.pgen.0030194

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.