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 (GWASs). DESIGN AND METHODS:Using genotypes from a GWAS focusing on obesity and thinness, quantitative trait association analyses (PLINK) for plasma uric acid levels in 1,060 extremely obese individuals (BMI > 35 kg/m2) and normal-weight controls (BMI < 25 kg/m2) were performed. 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 MICAL2 genes. Besides SLC2A9, three 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) , 550 K 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.

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