Polycyclic aromatic hydrocarbons exposure and hyperuricemia: insights from China-Northern Anhui Coal workers Cohort study to network toxicology analysis.

High prevalence of metabolic disease among coal workers has attracted particular attention. This study aims to investigate the relationship between urinary polycyclic aromatic hydrocarbons metabolites (OH-PAHs) and the risk of hyperuricaemia (HUA) by the baseline survey of the China-Northern Anhui Coal Workers Cohort (C-NACWC) study and explore the possible molecular mechanism. Basic information, lifestyle and occupational exposure of 2043 participants were collected via questionnaires. Serum and morning urine samples were collected simultaneously, and their urinary OH-PAHs were measured using GC-MS. In this study, 480 (23.5%) participants were diagnosed with HUA. Participants in the HUA group were younger and had a shorter work tenure, higher BMI and smoking index, and showed a dietary preference for heavy oil and salt. Logistic regression analysis suggested that 1-OHNA, 2-OHNA, 2-OHFLu and 1-OHPh contributed significantly to elevated risk of HUA after adjusting for confounding factors and false discovery rate (FDR) correction. Multivariate linear regression analysis showed that 2-OHNA and 2-OHFLu were positively correlated with uric acid concentration in serum. Notably, 1-OHNA and 2-OHNA had the highest weights among PAH metabolites in the weighted quantile sum (WQS) model and the Bayesian kernel machine regression (BKMR) model. Subgroup analysis revealed that elevated OH-PAHs were positively associated with the risk of HUA among tunneling, mining and underground auxiliary workers. Furthermore, network toxicology highlighted inflammation-related genes and IL-17 pathway as possible toxicological mechanism linking PAHs exposure and HUA. In conclusion, our findings underscore the significance of understanding the potential health risks associated with PAHs and emphasize that inflammation-related genes may be involved in the adverse effect of PAHs on HUA risk among coal workers.