The gender-specific association of the putative fructose transporter SLC2A9 variants with uric acid levels is modified by BMI

  1. Anita Brandstätter, PhD1,
  2. Stefan Kiechl, MD2,
  3. Barbara Kollerits, MSc1,
  4. Steven C. Hunt, PhD3,
  5. Iris M. Heid, PhD4,,5,
  6. Stefan Coassin, MSc1,
  7. Johann Willeit, MD2,
  8. Ted D. Adams, PhD3,
  9. Thomas Illig, PhD4,
  10. Paul N. Hopkins, MD MSPH3 and
  11. Florian Kronenberg, MD (Florian.Kronenberg{at}i-med.ac.at)1
  1. 1Division of Genetic Epidemiology; Department of Medical Genetics, Molecular and Clinical Pharmacology; Innsbruck Medical University, Innsbruck, Austria
  2. 2Department of Neurology, Innsbruck Medical University, Innsbruck, Austria
  3. 3Cardiovascular Genetics Division, University of Utah School of Medicine, Salt Lake City, UT, USA
  4. 4Institute of Epidemiology, Helmholtz Center Munich, German Research Center for Environmental Health, Neuherberg, Germany
  5. 5Institute of Information Management, Biometry and Epidemiology, Ludwig-Maximilians-University of Munich, Munich, Germany

    Abstract

    Objective: High serum uric acid (UA) levels lead to gout and were reported to be associated with an increased risk for hypertension, obesity, metabolic syndrome, type 2 diabetes mellitus and cardiovascular disease. Recently, the putative fructose transporter SLC2A9 was reported to influence UA levels. The aim of the present study was to examine the association of four single nucleotide polymorphisms (SNPs) within this gene with UA levels and whether this association is modified by obesity.

    Research Design and Methods: Four SNPs 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 1038 subjects recruited for severe obesity and 831 controls.

    Results: We observed highly significant associations between all four polymorphisms with UA levels in all study groups. Each copy of the minor allele decreased age- and gender-adjusted UA levels on average by 0.30-0.35 mg/dl 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 ranging from 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 UA levels and are modified by gender and BMI.

    Footnotes

      • Received February 18, 2008.
      • Accepted May 8, 2008.

    This Article

    1. Published online before print May 16, 2008, doi: 10.2337/dc08-0349
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