Sex-Specific Association of the Putative Fructose Transporter SLC2A9 Variants With Uric Acid Levels Is Modified by BMI
- Anita Brandstätter, PHD1,
- Stefan Kiechl, MD2,
- Barbara Kollerits, MSC1,
- Steven C. Hunt, PHD3,
- Iris M. Heid, PHD4,5,
- Stefan Coassin, MSC1,
- Johann Willeit, MD2,
- Ted D. Adams, PHD3,
- Thomas Illig, PHD4,
- Paul N. Hopkins, MD, MSPH3 and
- Florian Kronenberg, MD1
- 1Division of Genetic Epidemiology, Department of Medical Genetics, Molecular and Clinical Pharmacology, Innsbruck Medical University, Innsbruck, Austria
- 2Department of Neurology, Innsbruck Medical University, Innsbruck, Austria
- 3Cardiovascular Genetics Division, University of Utah School of Medicine, Salt Lake City, Utah
- 4Institute of Epidemiology, Helmholtz Center Munich, German Research Center for Environmental Health, Neuherberg, Germany
- 5Institute of Information Management, Biometry and Epidemiology, Ludwig-Maximilians-University of Munich, Munich, Germany
- Corresponding author: Florian Kronenberg, florian.kronenberg{at}i-med.ac.at
Abstract
OBJECTIVE—High serum uric acid levels lead to gout and have been reported to be associated with an increased risk of hypertension, obesity, metabolic syndrome, type 2 diabetes, and cardiovascular disease. Recently, the putative fructose transporter SLC2A9 was reported to influence uric acid levels. The aim of the present study was to examine the association of four single nucleotide polymorphisms within this gene with uric acid levels and to determine whether this association is modified by obesity.
RESEARCH DESIGN AND METHODS—Four single nucleotide polymorphisms within SLC2A9 (rs6855911, rs7442295, rs6449213, and rs12510549) were genotyped in the population-based prospective Bruneck Study (n = 800) and in a case-control study from Utah including 1,038 subjects recruited for severe obesity and 831 control subjects.
RESULTS—We observed highly significant associations between all four polymorphisms and uric acid levels in all study groups. Each copy of the minor allele decreased age- and sex-adjusted uric acid levels by 0.30–0.35 mg/dl on average, which translates to a relative decrease of 5–6% with P values ranging from 10−9 to 10−11 in the combined analysis. An extended adjustment for BMI, creatinine, gout medication, and alcohol intake improved P values to a range of 10−14 to 10−20. The association was more pronounced in women and the population-based Bruneck Study and was significantly modified by BMI, with stronger effect sizes in individuals with high BMI.
CONCLUSIONS—Genetic variants within SLC2A9 have significant effects on uric acid levels and are modified by sex and BMI.
Footnotes
-
Published ahead of print at http://care.diabetesjournals.org on 16 May 2008.
Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered. See http://creativecommons.org/licenses/by-nc-nd/3.0/ for details.
The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked “advertisement” in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
-
- Received February 18, 2008.
- Accepted May 8, 2008.
- DIABETES CARE
