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. Research: Design and 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 0.30-0.38mg/dL for SLC2A9 (p values: 10-20-10-36) and increased levels by 0.34mg/dL for ABCG2 (p=1.1×10-16). SLC17A3 influenced uric acid levels only modestly. Together the SNPs showed graded associations with uric acid levels of 0.111mg/dL per risk allele (p=3.8×10-42). 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. © 2009 Elsevier Ireland Ltd.