Association of single-nucleotide polymorphisms in SLC2A9, SLC22A12 and SLC22A11 genes with hyperuricemia in the Chinese Tibetan population.

Genome-wide association studies have identified a series of genes, including solute carrier family 2 member 9 (SLC2A9), solute carrier family 22 member 11 (SLC22A11), solute carrier family 22 member 12 (SLC22A12) polymorphisms, that are associated with serum uric acid (SUA) levels. The prevalence of hyperuricemia in the Chinese Tibetan population is higher than in other regions of China; however, there is no evidence confirming a genetic association with SUA levels in this population. This study aimed to investigate the association between genetic polymorphisms and SUA levels, as well as hyperuricemia, in a Tibetan population in Tibet, China. A total of 194 Tibetan patients with hyperuricemia and 304 healthy Tibetan controls were enrolled, and polymorphisms in SLC2A9 (rs1014290), SLC22A12 (rs559946), and SLC22A11 (rs1783811) were identified using high-resolution melting. Logistic regression analysis, with adjustments for age and gender, was applied to evaluate the association between genetic polymorphisms and the risk of hyperuricemia, while calculating the corresponding odds ratios (OR) and 95% confidence interval (CI). Linear regression analysis was used to calculate beta values for associations with higher SUA levels. We found no significant association between SLC2A9 (rs1014290), SLC22A12 (rs559946), SLC22A11 (rs1783811), and hyperuricemia in the Tibetan population. Among hyperuricemia patients, SLC22A12 (rs559946) was negatively correlated with SUA levels after adjusting for gender and age. Under the dominant model, the rs559946 CC genotype was a protective factor against higher SUA levels in hyperuricemia patients (CC vs CT + TT: OR = 0.379, 95% CI: 0.162-0.886, P = .025). Under the additive model, rs559946 was also a protective factor (OR = 0.385, 95% CI: 0.175-0.850, P = .018). This study is the first to demonstrate that the CC genotype of SLC22A12 (rs559946) reduces the risk of higher SUA in Chinese Tibetan patients with hyperuricemia.