SLC2A9 influences uric acid concentrations with pronounced sex-specific effects

Nat Genet. 2008 Apr;40(4):430-6. doi: 10.1038/ng.107. Epub 2008 Mar 9.

Abstract

Serum uric acid concentrations are correlated with gout and clinical entities such as cardiovascular disease and diabetes. In the genome-wide association study KORA (Kooperative Gesundheitsforschung in der Region Augsburg) F3 500K (n = 1,644), the most significant SNPs associated with uric acid concentrations mapped within introns 4 and 6 of SLC2A9, a gene encoding a putative hexose transporter (effects: -0.23 to -0.36 mg/dl per copy of the minor allele). We replicated these findings in three independent samples from Germany (KORA S4 and SHIP (Study of Health in Pomerania)) and Austria (SAPHIR; Salzburg Atherosclerosis Prevention Program in Subjects at High Individual Risk), with P values ranging from 1.2 x 10(-8) to 1.0 x 10(-32). Analysis of whole blood RNA expression profiles from a KORA F3 500K subgroup (n = 117) showed a significant association between the SLC2A9 isoform 2 and urate concentrations. The SLC2A9 genotypes also showed significant association with self-reported gout. The proportion of the variance of serum uric acid concentrations explained by genotypes was about 1.2% in men and 6% in women, and the percentage accounted for by expression levels was 3.5% in men and 15% in women.

Publication types

  • Multicenter Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Austria
  • Biomarkers / blood
  • Case-Control Studies
  • Computational Biology
  • Female
  • Genome, Human*
  • Genotype
  • Germany
  • Glucose Transport Proteins, Facilitative / genetics*
  • Gout / genetics*
  • Humans
  • Male
  • Middle Aged
  • Polymorphism, Single Nucleotide / genetics*
  • Sex Distribution
  • Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization
  • Uric Acid / blood*

Substances

  • Biomarkers
  • Glucose Transport Proteins, Facilitative
  • SLC2A9 protein, human
  • Uric Acid