SLC2A9 influences uric acid concentrations with pronounced sex-specific effects

• Published in: Nature genetics Vol. 40; no. 4; pp. 430 - 436
• Main Authors: Döring, Angela, Gieger, Christian, Mehta, Divya, Gohlke, Henning, Prokisch, Holger, Coassin, Stefan, Fischer, Guido, Henke, Kathleen, Klopp, Norman, Kronenberg, Florian, Paulweber, Bernhard, Pfeufer, Arne, Rosskopf, Dieter, Völzke, Henry, Illig, Thomas, Meitinger, Thomas, Wichmann, H-Erich, Meisinger, Christa
• Format: Journal Article
• Language: English
• Published: New York Nature Publishing Group US 01.04.2008; Nature Publishing Group
• Subjects: Acids; Adult; Aged; Aged, 80 and over; Agriculture; Animal Genetics and Genomics; Austria; Biological and medical sciences; Biomarkers - blood; Biomedical and Life Sciences; Biomedicine; Blood; Blood tests; Cancer Research; Cardiovascular diseases; Case-Control Studies; Complications and side effects; Computational Biology; Female; Fundamental and applied biological sciences. Psychology; Gender differences; Gene expression; Gene Function; Genetic aspects; Genetics of eukaryotes. Biological and molecular evolution; Genome, Human; Genomics; Genotype; Genotype & phenotype; Genotypes; Germany; Glucose Transport Proteins, Facilitative - genetics; Gout; Gout - genetics; Human Genetics; Humans; Hyperuricemia; letter; Male; Middle Aged; Polymorphism, Single Nucleotide - genetics; Prevention; Ribonucleic acid; Risk factors; RNA; Sex Distribution; Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; Uric Acid - blood; Austria; Germany; Sex; Uric acid; Concentration
• ISSN: 1061-4036; 1546-1718; 1546-1718
• DOI: 10.1038/ng.107

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 × 10 −8 to 1.0 × 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.