PLoS Genetics (Nov 2007)

The GLUT9 gene is associated with serum uric acid levels in Sardinia and Chianti cohorts.

  • Siguang Li,
  • Serena Sanna,
  • Andrea Maschio,
  • Fabio Busonero,
  • Gianluca Usala,
  • Antonella Mulas,
  • Sandra Lai,
  • Mariano Dei,
  • Marco Orrù,
  • Giuseppe Albai,
  • Stefania Bandinelli,
  • David Schlessinger,
  • Edward Lakatta,
  • Angelo Scuteri,
  • Samer S Najjar,
  • Jack Guralnik,
  • Silvia Naitza,
  • Laura Crisponi,
  • Antonio Cao,
  • Gonçalo Abecasis,
  • Luigi Ferrucci,
  • Manuela Uda,
  • Wei-Min Chen,
  • Ramaiah Nagaraja

DOI
https://doi.org/10.1371/journal.pgen.0030194
Journal volume & issue
Vol. 3, no. 11
p. e194

Abstract

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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.