Gene Dose-Dependent and Additive Effects of ABCG2 rs2231142 and SLC2A9 rs3733591 Genetic Polymorphisms on Serum Uric Acid Levels

Abstract

This study aimed to evaluate whether the single nucleotide polymorphisms of ATP-binding cassette subfamily G member 2 (ABCG2) and solute carrier family 2 member 9 (SLC2A9) affect individual blood uric acid levels using pyrosequencing. ABCG2 (rs2231142, rs72552713, rs2231137), SLC2A9 (rs3734553, rs3733591, rs16890979), and individual uric acid levels were prospectively analyzed in 250 healthy young Korean male participants. Prominent differences in uric acid levels of the alleles were observed in the SLC2A9 rs3733591 polymorphism: wild-type (AA) vs. heterozygote (AG), 0.7 mg/dL (p < 0.0001); AA vs. mutant type (GG), 1.32 mg/dL (p < 0.0001); and AG vs. GG, 0.62 mg/dL (p < 0.01). In ABCG2 single nucleotide polymorphisms (SNPs), the statistically significant differences in uric acid levels were only found in rs2231142 between CC vs. AA (1.06 mg/dL; p < 0.001), and CC vs. CA (0.59 mg/dL; p < 0.01). Serum uric acid levels based on the ABCG2 and SLC2A9 diplotype groups were also compared. The uric acid levels were the lowest in the CC/AA diplotype and highest in the AA/AG diplotype. In addition, the SNP SLC2A9 rs3733591 tended to increase the uric acid levels when the ABCG2 rs2231142 haplotypes were fixed. In conclusion, both the ABCG2 rs2231142 and SLC2A9 rs3733591 polymorphisms may additively elevate blood uric acid levels.