title: Sex and age interaction with genetic association of atherogenic uric acid concentrations.
abstract: BACKGROUND
  High serum uric acid levels are associated with gout, atherosclerosis and cardiovascular disease. Three genes (SLC2A9, ABCG2, and SLC17A3) were reported to be involved in the regulation of uric acid levels.
  
  
  METHODS
  
  
  
  METHODS
  SNPs rs2231142 (ABCG2) and rs1165205 (SLC17A3) were genotyped in three cohorts (n=4492) and combined with previously genotyped SNPs within SLC2A9 (rs6855911, rs7442295, rs6449213, rs12510549).
  
  
  RESULTS
  Each copy of the minor allele decreased uric acid levels by 0.30-0.38 mg/dL for SLC2A9 (p values: 10(-20)-10(-36)) and increased levels by 0.34 mg/dL for ABCG2 (p=1.1x10(-16)). SLC17A3 influenced uric acid levels only modestly. Together the SNPs showed graded associations with uric acid levels of 0.111 mg/dL per risk allele (p=3.8x10(-42)). In addition, we observed a sex-specific interaction of age with the association of SLC2A9 SNPs with uric acid levels, where increasing age strengthened the association of SNPs in women and decreased the association in men.
  
  
  CONCLUSIONS
  Genetic variants within SLC2A9,ABCG2 and SLC17A3 show highly significant associations with uric acid levels, and for SNPs within SLC2A9 this association is strongly modified by age and sex.
authors.affiliation: Division of Genetic Epidemiology, Department of Medical Genetics, Molecular and Clinical Pharmacology, Innsbruck Medical University, Schöpfstr. 41, A-6020 Innsbruck, Austria.
authors.forename: Anita
authors.initials: A
authors.lastname: Brandstätter
authors.forename: Claudia
authors.initials: C
authors.lastname: Lamina
authors.forename: Stefan
authors.initials: S
authors.lastname: Kiechl
authors.forename: Steven C
authors.initials: SC
authors.lastname: Hunt
authors.forename: Stefan
authors.initials: S
authors.lastname: Coassin
authors.forename: Bernhard
authors.initials: B
authors.lastname: Paulweber
authors.forename: Felix
authors.initials: F
authors.lastname: Kramer
authors.forename: Monika
authors.initials: M
authors.lastname: Summerer
authors.forename: Johann
authors.initials: J
authors.lastname: Willeit
authors.forename: Lyudmyla
authors.initials: L
authors.lastname: Kedenko
authors.forename: Ted D
authors.initials: TD
authors.lastname: Adams
authors.forename: Florian
authors.initials: F
authors.lastname: Kronenberg
mesh_terms: D000070997:ATP Binding Cassette Transporter, Subfamily G, Member 2; D018528:ATP-Binding Cassette Transporters / Q000235:genetics; D000367:Age Factors; D000368:Aged; D050197:Atherosclerosis / Q000453:epidemiology* / Q000378:metabolism; D002318:Cardiovascular Diseases / Q000453:epidemiology* / Q000378:metabolism; D015331:Cohort Studies; D005260:Female; D005838:Genotype; D051246:Glucose Transport Proteins, Facilitative / Q000235:genetics; D006073:Gout / Q000453:epidemiology* / Q000378:metabolism; D006801:Humans; D008297:Male; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000235:genetics; D020641:Polymorphism, Single Nucleotide; D012737:Sex Factors; D050609:Sodium-Phosphate Cotransporter Proteins, Type I / Q000235:genetics; D014527:Uric Acid / Q000378:metabolism*
chemical_list: C116614:ABCG2 protein, human; D000070997:ATP Binding Cassette Transporter, Subfamily G, Member 2; D018528:ATP-Binding Cassette Transporters; D051246:Glucose Transport Proteins, Facilitative; D009363:Neoplasm Proteins; C493550:SLC17A3 protein, human; C411811:SLC2A9 protein, human; D050609:Sodium-Phosphate Cotransporter Proteins, Type I; D014527:Uric Acid