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Common Polymorphisms Influencing Serum Uric Acid Levels Contribute to Susceptibility to Gout, but Not to Coronary Artery Disease

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  • Klaus Stark
  • Wibke Reinhard
  • Martina Grassl
  • Jeanette Erdmann
  • Heribert Schunkert
  • Thomas Illig
  • Christian Hengstenberg

Abstract

Background: Recently, a large meta-analysis including over 28,000 participants identified nine different loci with association to serum uric acid (UA) levels. Since elevated serum UA levels potentially cause gout and are a possible risk factor for coronary artery disease (CAD) and myocardial infarction (MI), we performed two large case-control association analyses with participants from the German MI Family Study. In the first study, we assessed the association of the qualitative trait gout and ten single nucleotide polymorphisms (SNP) markers that showed association to UA serum levels. In the second study, the same genetic polymorphisms were analyzed for association with CAD. Methods and Findings: A total of 683 patients suffering from gout and 1,563 healthy controls from the German MI Family Study were genotyped. Nine SNPs were identified from a recently performed genome-wide meta-analysis on serum UA levels (rs12129861, rs780094, rs734553, rs2231142, rs742132, rs1183201, rs12356193, rs17300741 and rs505802). Additionally, the marker rs6855911 was included which has been associated with gout in our cohort in a previous study. SNPs rs734553 and rs6855911, located in SLC2A9, and SNP rs2231142, known to be a missense polymorphism in ABCG2, were associated with gout (p = 5.6*10−7, p = 1.1*10−7, and p = 1.3*10−3, respectively). Other SNPs in the genes PDZK1, GCKR, LRRC16A, SLC17A1-SLC17A3, SLC16A9, SLC22A11 and SLC22A12 failed the significance level. None of the ten markers were associated with risk to CAD in our study sample of 1,473 CAD cases and 1,241 CAD-free controls. Conclusion: SNP markers in SLC2A9 and ABCG2 genes were found to be strongly associated with the phenotype gout. However, not all SNP markers influencing serum UA levels were also directly associated with the clinical manifestation of gout in our study sample. In addition, none of these SNPs showed association with the risk to CAD in the German MI Family Study.

Suggested Citation

  • Klaus Stark & Wibke Reinhard & Martina Grassl & Jeanette Erdmann & Heribert Schunkert & Thomas Illig & Christian Hengstenberg, 2009. "Common Polymorphisms Influencing Serum Uric Acid Levels Contribute to Susceptibility to Gout, but Not to Coronary Artery Disease," PLOS ONE, Public Library of Science, vol. 4(11), pages 1-7, November.
    • Handle: RePEc:plo:pone00:0007729
    DOI: 10.1371/journal.pone.0007729
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    1. Melanie Kolz & Toby Johnson & Serena Sanna & Alexander Teumer & Veronique Vitart & Markus Perola & Massimo Mangino & Eva Albrecht & Chris Wallace & Martin Farrall & Åsa Johansson & Dale R Nyholt & Yur, 2009. "Meta-Analysis of 28,141 Individuals Identifies Common Variants within Five New Loci That Influence Uric Acid Concentrations," PLOS Genetics, Public Library of Science, vol. 5(6), pages 1-10, June.
    2. B. Devlin & Kathryn Roeder, 1999. "Genomic Control for Association Studies," Biometrics, The International Biometric Society, vol. 55(4), pages 997-1004, December.
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