title: The GLUT9 gene is associated with serum uric acid levels in Sardinia and Chianti cohorts.
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.
authors.affiliation: Laboratory of Genetics, National Institute on Aging, Baltimore, Maryland, United States of America.
authors.forename: Siguang
authors.initials: S
authors.lastname: Li
authors.forename: Serena
authors.initials: S
authors.lastname: Sanna
authors.forename: Andrea
authors.initials: A
authors.lastname: Maschio
authors.forename: Fabio
authors.initials: F
authors.lastname: Busonero
authors.forename: Gianluca
authors.initials: G
authors.lastname: Usala
authors.forename: Antonella
authors.initials: A
authors.lastname: Mulas
authors.forename: Sandra
authors.initials: S
authors.lastname: Lai
authors.forename: Mariano
authors.initials: M
authors.lastname: Dei
authors.forename: Marco
authors.initials: M
authors.lastname: Orrù
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Albai
authors.forename: Stefania
authors.initials: S
authors.lastname: Bandinelli
authors.forename: David
authors.initials: D
authors.lastname: Schlessinger
authors.forename: Edward
authors.initials: E
authors.lastname: Lakatta
authors.forename: Angelo
authors.initials: A
authors.lastname: Scuteri
authors.forename: Samer S
authors.initials: SS
authors.lastname: Najjar
authors.forename: Jack
authors.initials: J
authors.lastname: Guralnik
authors.forename: Silvia
authors.initials: S
authors.lastname: Naitza
authors.forename: Laura
authors.initials: L
authors.lastname: Crisponi
authors.forename: Antonio
authors.initials: A
authors.lastname: Cao
authors.forename: Gonçalo
authors.initials: G
authors.lastname: Abecasis
authors.forename: Luigi
authors.initials: L
authors.lastname: Ferrucci
authors.forename: Manuela
authors.initials: M
authors.lastname: Uda
authors.forename: Wei-Min
authors.initials: WM
authors.lastname: Chen
authors.forename: Ramaiah
authors.initials: R
authors.lastname: Nagaraja
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015331:Cohort Studies; D005260:Female; D015894:Genome, Human / Q000235:genetics; D005838:Genotype; D051246:Glucose Transport Proteins, Facilitative / Q000235:genetics*; D006801:Humans; D007558:Italy; D015810:Linkage Disequilibrium; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D014527:Uric Acid / Q000097:blood*
chemical_list: D051246:Glucose Transport Proteins, Facilitative; C411811:SLC2A9 protein, human; D014527:Uric Acid