Association between SLC2A9 transporter gene variants and uric acid phenotypes in African American and white families

Methods. Genotypes of single nucleotide polymorphisms (SNPs) distributed across the SLC2A9 gene were obtained in the Genetic Epidemiology Network of Arteriopathy cohorts. The associations of SNPs with serum uric acid, fractional excretion of urate and urine urate-to-creatinine ratio were assessed with adjustments for age, sex, diuretic use, BMI, homocysteine and triglycerides. Results. We identified SLC2A9 gene variants that were associated with serum uric acid in 1155 African American subjects (53 SNPs) and 1132 white subjects (63 SNPs). The most statistically significant SNPs in African American subjects (rs13113918) and white subjects (rs11723439) were in the latter half of the gene and explained 2.7 and 2.8% of the variation in serum uric acid, respectively. After adjustment for this SNP in African Americans, 0.9% of the variation in serum uric acid was explained by an SNP (rs1568318) in the first half of the gene. Unexpectedly, SLC2A9 gene variants had stronger associations with serum uric acid than with fractional excretion of urate. Conclusions. These findings support two different loci by which SLC2A9 variants affect uric acid levels in African Americans and suggest SLC2A9 variants affect serum uric acid level via renal and extrarenal clearance.