SLC2A9 Gene Polymorphism Is Associated with Elevated Serum Uric Acid Caused by Pyrazinamide

Abstract

What Is Known and Objective. Elevated serum uric acid (SUA) is one of the most common adverse reactions during the administration of pyrazinamide, but patients exhibit significant individual differences. This study aimed to evaluate the relationship between gene polymorphisms and pyrazinamide-induced SUA elevation in Han Chinese tuberculosis patients. Methods. Tuberculosis patients treated with pyrazinamide were genotyped for the following three candidate genes: SLC22A12, SLC2A9, and ABCG2. Patients were divided into low-risk and high-risk groups according to the change of SUA after treatment. Intergroup comparisons were performed on clinical characteristics, allele and genotype frequencies, and haplotype distributions, and logistic regression analysis was used to explore the relevant risk factors. Results. In total, 143 patients were enrolled, including 83 in the high-risk groups and 60 in the low-risk groups. We observed a significant association between SLC2A9 polymorphism and pyrazinamide-induced SUA elevation. The G allele was significantly lower in the high-risk group than in the low-risk group (27.7% vs. 48.3%, OR = 0.410, 95% CI: 0.250–0.671, $p<0.001$ ). Patients with the GA and GG genotypes were less likely to have SUA elevation than those with the AA genotype (OR = 0.125, 95% CI: 0.053–0.293, $p<0.001$ and OR = 0.252, 95% CI: 0.074–0.851, $p=0.026$ , respectively). Regarding SLC2A9 rs13129697, the frequency of the G allele was significantly lower in the high-risk group than in the low-risk group (26.1% vs. 40.8%, OR = 0.531, 95% CI: 0.312–0.842, $p=0.008$ ). In the low-risk group, the proportion of patients with the TG genotype was significantly higher than that with the TT genotype (81.7% vs. 18.3%, OR = 0.279, 95% CI: 0.127–0.611, $p=0.001$ ). Haplotype analysis revealed that patients with the SLC2A9 (rs1014290–rs13129697) GG haplotype had lower risk of SUA elevation than those with the AT haplotype (27.11% vs. 63.25%, $p=0.005$ ). Furthermore, logistic regression analysis showed that drinking history was an independent risk factor for elevated SUA caused by PZA (OR = 3.943, 95% CI = 1.18–13.175, $p=0.026$ ) and that the rs1014290 GA genotype might be a protective factor (OR = 0.094, 95% CI = 0.023–0.386, $p=0.001$ ) after correction. What Is New and Conclusion. We found that SLC2A9 genetic polymorphisms were associated with elevated SUA caused by pyrazinamide. The G>A variant of rs1014290 and drinking history might be risk factors.