Serum uric acid and the risk of MASLD in Americans: A cross-sectional study combined with Mendelian randomization and network toxicology analysis

Serum uric acid (SUA) is the end product of purine metabolism, and its elevated levels are closely associated with a variety of metabolic disorders. Although some studies have mentioned the possible link between SUA and metabolic dysfunction-associated steatotic liver disease (MASLD), no study has yet clearly defined the inevitable association between the 2. This study aims to provide evidence of the association between the 2 and explore their targets of action based on network toxicology. Weighted multivariate-adjusted logistic regression was employed to assess the relationship between SUA and the risk of MASLD. A two-sample Mendelian randomization (MR) study was conducted to further corroborate the causal relationship between SUA and MASLD. Inverse variance weighting (IVW) was used as the primary MR analysis method, with other supplementary MR methods aiding in validating the result. Further explored the toxic action targets of SUA on MASLD based on network toxicology analysis. The weighted multivariate-adjusted logistic regression analysis revealed a positive correlation between SUA and the risk of MASLD [odds ratio (OR) = 1.300; 95% confidence intervals (CI) = 1.175-1.438]. Additionally, SUA was independently associated with the median control attenuation parameter (CAP) (OR = 17,032.865, 95% CI = 1722.045-168,473.206). The results of the MR analysis also supported a causal relationship between SUA and MASLD (OR = 1.242; 95% CI = 1.060-1.454). Furthermore, molecular blind docking revealed the specific binding interactions and sites between SUA and target proteins. SUA is associated with an increased risk of MASLD incidence. Toxicological molecular docking simulation results show significant binding specificity between SUA components and target genes. The next step could be to develop preventive and screening programs for MASLD targeting individuals with high levels of SUA.