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 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.
Li
Siguang
S
Laboratory of Genetics, National Institute on Aging, Baltimore, Maryland, United States of America.
Sanna
Serena
S
Maschio
Andrea
A
Busonero
Fabio
F
Usala
Gianluca
G
Mulas
Antonella
A
Lai
Sandra
S
Dei
Mariano
M
Orrù
Marco
M
Albai
Giuseppe
G
Bandinelli
Stefania
S
Schlessinger
David
D
Lakatta
Edward
E
Scuteri
Angelo
A
Najjar
Samer S
SS
Guralnik
Jack
J
Naitza
Silvia
S
Crisponi
Laura
L
Cao
Antonio
A
Abecasis
Gonçalo
G
Ferrucci
Luigi
L
Uda
Manuela
M
Chen
Wei-Min
WM
Nagaraja
Ramaiah
R
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*
D051246:Glucose Transport Proteins, Facilitative; C411811:SLC2A9 protein, human; D014527:Uric Acid