SLC2A9 influences uric acid concentrations with pronounced sex-specific effects

• DOI: 10.1038/ng.107
• Publication Date: 2008-03-09T19:43:39Z
• Authors: Angela Döring; Christian Gieger; Divya Mehta; Henning Gohlke; Holger Prokisch; Stefan Coassin; Guido Fischer; Kathleen Henke; Norman Klopp; Florian Kronenberg; Bernhard Paulweber; Arne Pfeufer; Dieter Rosskopf; Henry Völzke; Thomas Illig; Thomas Meitinger; H-Erich Wichmann; Christa Meisinger
• Keywords: Adult; Male; hypertension; Genotype; Gout; Glucose Transport Proteins, Facilitative; 610; Polymorphism, Single Nucleotide; 03 medical and health sciences; uric acid; Germany; Humans; Sex Distribution; sodium; Aged; Aged, 80 and over; 0303 health sciences; Genome, Human; blood pressure; Computational Biology; Middle Aged; Uric Acid; 3. Good health; Austria; Case-Control Studies; Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; urate; Female; Biomarkers

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.