Letter abstract
Nature Genetics 40, 430 - 436 (2008)
Published online: 9 March 2008 | doi:10.1038/ng.107
SLC2A9 influences uric acid concentrations with pronounced sex-specific effects
Angela Döring1,10, Christian Gieger1,2,10, Divya Mehta3, Henning Gohlke1, Holger Prokisch3,4, Stefan Coassin5, Guido Fischer1, Kathleen Henke6, Norman Klopp1,2, Florian Kronenberg5, Bernhard Paulweber7, Arne Pfeufer3,4, Dieter Rosskopf6, Henry Völzke8, Thomas Illig1, Thomas Meitinger3,4, H-Erich Wichmann1,2 & Christa Meisinger1,9
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.
- Institute of Epidemiology, Helmholtz Zentrum München, German Research Center for Environmental Health, 85764 Neuherberg, Germany.
- Institute of Medical Informatics, Biometry and Epidemiology, Ludwig-Maximilians-Universität, 81377 Munich, Germany.
- Institute of Human Genetics, Helmholtz Zentrum München, German Research Center for Environmental Health, 85764 Neuherberg, Germany.
- Institute of Human Genetics, Klinikum rechts der Isar, Technical University Munich, 81765 Munich, Germany.
- Division of Genetic Epidemiology, Department of Medical Genetics, Molecular and Clinical Pharmacology, Innsbruck Medical University, 6020 Innsbruck, Austria.
- Department of Pharmacology, Ernst-Moritz-Arndt University, 17487 Greifswald, Germany.
- First Department of Internal Medicine, St. Johann Spital, Paracelsus Private Medical University, 5020 Salzburg, Austria.
- Institute for Community Medicine, Ernst-Moritz-Arndt University, 17487 Greifswald, Germany.
- Central Hospital of Augsburg, MONICA (Monitoring Trends and Determinants of Cardiovascular Disease)/KORA (Kooperative Gesundheitsforschung in der Region Augsburg) Myocardial Infarction Registry, 86156 Augsburg, Germany.
- These authors contributed equally to this work.
Correspondence to: Christa Meisinger1,9 e-mail: christa.meisinger@helmholtz-muenchen.de
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