Association between combined exposure to ambient air pollutants, genetic risk, and incident gout risk: A prospective cohort study in the UK Biobank

Limited research has been conducted on the association between long-term exposure to air pollutants and the incidence of gout. This study aims to assess the individual and combined effects of prolonged exposure to five air pollutants (NO2, NOx, PM10, PMcoarse and PM2.51) on the incidence of gout among 458,884 initially gout-free participants enrolled in the UK Biobank. Employing a land use regression model, we utilized an estimation method to ascertain the annual concentrations of the five air pollutants. Subsequently, we devised a weighted air pollution score to facilitate a comprehensive evaluation of exposure. The Cox proportional hazards model was utilized to investigate the association between ambient air pollution and gout risk. Interaction and stratification analyses were conducted to evaluate age, sex, BMI, and genetic predisposition as potential effect modifiers in the air pollution-gout relationship. Furthermore, mediation analyses were conducted to explore the potential involvement of biomarkers in mediating the association between air pollution and gout. Over a median follow-up time of 12.0 years, 7,927 cases of gout were diagnosed. Significant associations were observed between the risk of gout and a per IQR increase in NO2 (HR2: 1.05, 95% CI3: 1.02-1.08, p=0.003), NOx (HR: 1.04, 95% CI: 1.01-1.06, p=0.003), and PM2.5 (HR: 1.03, 95% CI: 1.00-1.06, p=0.030). Per IQR increase in the air pollution score was associated with an elevated risk of gout (p=0.005). Stratified analysis revealed a significant correlation between the air pollution score and gout risk in participants ≥60 years (HR: 1.05, 95% CI: 1.02-1.09, p=0.005), but not in those <60 years (p=0.793), indicating a significant interaction effect with age (P-interaction=0.009). Mediation analyses identified five serum biomarkers (SUA:15.87%, VITD: 5.04%, LDLD: 3.34%, GGT: 1.90%, AST: 1.56%4) with potential mediation effects on this association. Long-term exposure to air pollutants, particularly among the elderly population, is associated with an increased risk of developing gout. The underlying mechanisms of these associations may involve the participation of five serum biomarkers.