title: Association of common polymorphisms in GLUT9 gene with gout but not with coronary artery disease in a large case-control study.
abstract: BACKGROUND
  Serum uric acid (UA) levels have recently been shown to be genetically influenced by common polymorphisms in the GLUT9 gene in two genome-wide association analyses of Italian and British populations. Elevated serum UA levels are often found in conjunction with the metabolic syndrome. Hyperuricemia is the major risk factor for gout and has been associated with increased cardiovascular morbidity and mortality. The aim of the present study was to further elucidate the association of polymorphisms in GLUT9 with gout and coronary artery disease (CAD) or myocardial infarction (MI). To test our hypotheses, we performed two large case-control association analyses of individuals from the German MI Family Study.
  
  
  RESULTS
  First, 665 patients with gout and 665 healthy controls, which were carefully matched for age and gender, were genotyped for four single nucleotide polymorphisms (SNPs) within or near the GLUT9 gene. All four SNPs demonstrated highly significant association with gout. SNP rs6855911, located within intron 7 of GLUT9, showed the strongest signal with a protective effect of the minor allele with an allelic odds ratio of 0.62 (95% confidence interval 0.52-0.75; p = 3.2*10(-7)). Importantly, this finding was not influenced by adjustment for components of the metabolic syndrome or intake of diuretics. Secondly, 1,473 cases with severe CAD or MI and 1,241 healthy controls were tested for the same four GLUT9 SNPs. The analyses revealed, however, no significant association with CAD or with MI. Additional screening of genome-wide association data sets showed no signal for CAD or MI within the GLUT9 gene region.
  
  
  CONCLUSIONS
  Thus, our results provide compelling evidence that common genetic variations within the GLUT9 gene strongly influence the risk for gout but are unlikely to have a major effect on CAD or MI in a German population.
authors.affiliation: Klinik und Poliklinik für Innere Medizin II, Klinikum der Universität Regensburg, Regensburg, Germany.
authors.forename: Klaus
authors.initials: K
authors.lastname: Stark
authors.forename: Wibke
authors.initials: W
authors.lastname: Reinhard
authors.forename: Katharina
authors.initials: K
authors.lastname: Neureuther
authors.forename: Silke
authors.initials: S
authors.lastname: Wiedmann
authors.forename: Kamil
authors.initials: K
authors.lastname: Sedlacek
authors.forename: Andrea
authors.initials: A
authors.lastname: Baessler
authors.forename: Marcus
authors.initials: M
authors.lastname: Fischer
authors.forename: Stefan
authors.initials: S
authors.lastname: Weber
authors.forename: Bernhard
authors.initials: B
authors.lastname: Kaess
authors.forename: Jeanette
authors.initials: J
authors.lastname: Erdmann
authors.forename: Heribert
authors.initials: H
authors.lastname: Schunkert
authors.forename: Christian
authors.initials: C
authors.lastname: Hengstenberg
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D016022:Case-Control Studies; D003324:Coronary Artery Disease / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease; D051246:Glucose Transport Proteins, Facilitative / Q000235:genetics*; D006073:Gout / Q000235:genetics*; D006801:Humans; D008297:Male; D024821:Metabolic Syndrome / Q000235:genetics; D008875:Middle Aged; D009203:Myocardial Infarction / Q000235:genetics; D011110:Polymorphism, Genetic; D020641:Polymorphism, Single Nucleotide; D014527:Uric Acid / Q000097:blood
chemical_list: D051246:Glucose Transport Proteins, Facilitative; C411811:SLC2A9 protein, human; D014527:Uric Acid