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

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 quanti...

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Veröffentlicht in:PLoS genetics Jg. 3; H. 11; S. e194
Hauptverfasser: 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
Sprache:Englisch
Veröffentlicht: United States Public Library of Science 01.11.2007
Public Library of Science (PLoS)
Schlagworte:
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
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Zusammenfassung: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.
Bibliographie:ObjectType-Article-1
SourceType-Scholarly Journals-1
ObjectType-Feature-2
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ISSN:1553-7404
1553-7390
1553-7404
DOI:10.1371/journal.pgen.0030194