Effects of occupational exposure factors interacting with NLRP3 gene polymorphisms on mild cognitive impairment: A cross-sectional study of workers in an aluminum electrolysis production environment

Mild cognitive impairment (MCI) is an early stage of Alzheimer's disease and is the result of interactions between environmental and genetic factors. However, their impact on aluminum workers is not yet clear. This study aimed to explore the interaction between occupational exposure and NLRP3 gene polymorphisms on the odds of MCI among aluminum production workers. We assessed the cognitive function of 478 workers in a factory in Guangxi, China, and identified two main occupational exposure factors: principal component 1 (PC1: noise, high temperature, carbon monoxide, sulfur dioxide, nitrogen oxides) and principal component 2 (PC2: aluminum oxide dust, magnetic field, fluoride, manganese dioxide). Genotyping of polymorphisms in the NLRP3 gene (rs10754558, rs10925027, rs3806265, rs4612666) was performed. The results of the analysis showed that high PC2 exposure significantly increased the odds of MCI [OR (95% CI): 1.99 (1.36, 2.91)], and the rs10754558 G/C genotype was independently associated with MCI [OR (95% CI): 1.56 (1.05, 2.33)]. PC2 interacted with rs3806265 C/T [OR (95% CI):2.13 (1.16, 3.92)] and rs4612666 C/T [OR (95% CI): 2.84 (1.19,6.81)], further increasing the odds of MCI. These findings suggest that alumina dust, magnetic fields, fluoride, and manganese dioxide are the main occupational hazards factors for MCI. rs10754558 G/C is an independent susceptibility genotype for MCI, while rs3806265 C/T and rs4612666 C/T are environmental susceptibility genotypes for MCI. This study emphasizes that reducing occupational exposure and screening for susceptibility genes can provide a basis for targeted interventions to reduce the odds of MCI in this population.