A genome wide association study of plasma uric acid levels in obese cases and never-overweight controls

OBJECTIVE: To identify plasma uric acid related genes in extremely obese and normal weight individuals using genome wide association studies (GWAS). DESIGN AND METHODS: Using genotypes from a GWAS focusing on obesity and thinness, we performed quantitative trait association analyses (PLINK) for plasma uric acid levels in 1,060 extremely obese individuals [body mass index (BMI) >35 kg/m(2)] and normal-weight controls (BMI<25kg/m(2)). In 961 samples with uric acid data, 924 were females. RESULTS: Significant associations were found in SLC2A9 gene SNPs and plasma uric acid levels (rs6449213, P=3.15×10(−12)). DIP2C gene SNP rs877282 also reached genome wide significance(P=4,56×10(−8)). Weaker associations (P<1×10(−5)) were found in F5, PXDNL, FRAS1, LCORL, and MICAL2genes. Besides SLC2A9, 3 previously identified uric acid related genes ABCG2 (rs2622605, P=0.0026), SLC17A1 (rs3799344, P=0.0017), and RREB1 (rs1615495, P =0.00055) received marginal support in our study. CONCLUSIONS: Two genes/chromosome regions reached genome wide association significance (P< 1× 10(−7), 550K SNPs) in our GWAS : SLC2A9, the chromosome 2 60.1 Mb region (rs6723995), and the DIP2C gene region. Five other genes (F5, PXDNL, FRAS1, LCORL, and MICAL2) yielded P<1× 10(−5). Four previous reported associations were replicated in our study, including SLC2A9, ABCG2, RREB, and SLC17A1.