Air Pollution, Genetic Susceptibility, and Risk of Incident Systemic Lupus Erythematosus: A Prospective Cohort Study

Abstract

Objective: There are few existing studies that investigate the risk of systemic lupus erythematosus (SLE) associated with long-term exposure to air pollutants. This study aimed to explore associations between long-term exposure to air pollutants and incident SLE and further evaluate interactions and joint effects of genetic risk and air pollutants.

Methods: A total of 459,815 participants were included from UK Biobank. The concentrations of air pollutants (fine particulate matter with diameter ≤2.5 μm [PM_2.5], particulate matter diameter ≤10 μm [PM₁₀], nitrogen dioxide [NO₂], and nitrogen oxides [NO_x]) were estimated by land-use regression model. We applied Cox proportional hazards model to explore linkages of air pollutants and incident SLE. The polygenic risk score (PRS) was used for further assessing the interactions and joint effects of genetic risk and air pollutants.

Results: A total of 399 patients with SLE were identified during a median follow-up of 11.77 years. There were positive associations between air pollutant exposure and incident SLE, as the adjusted hazard ratios were 1.18 (95% confidence interval [95% CI] 1.06-1.32), 1.23 (1.10-1.39), 1.27 (1.14-1.41), and 1.13 (1.03-1.23) for each interquartile range increase in PM_2.5, PM₁₀, NO₂, and NO_x, respectively. Moreover, participants with high genetic risk and high air pollution exposure had the highest risk of incident SLE compared with those with low genetic risk and low air pollution exposure (adjusted hazard ratio: PM_2.5, 4.16 [95% CI 2.67-6.49]; PM₁₀, 5.31 [95% CI 3.30,-8.55]; NO₂, 5.61 [95% CI 3.45-9.13]; and NO_x, 4.80 [95% CI 3.00-7.66]). There was a significant multiplicative interaction between NO₂ and PRS.

Conclusion: Long-term exposure to air pollutants (PM_2.5, PM₁₀, NO₂, and NO_x) may increase the risk of developing SLE.