Association between serum metal levels and NLRP3 gene polymorphisms with cognitive function in aluminum workers: A combined epidemiological and genetic study

Abstract

Background: Metals, genes, and cognitive function are closely related. This study evaluated serum metal levels, NLRP3 gene polymorphisms, and their association with cognitive function in aluminum workers.

Methods: A cross-sectional survey was conducted with 478 aluminum workers. Serum metal levels were measured using Inductively Coupled Plasma Mass Spectrometry (ICP-MS), and cognitive function was assessed using the Montreal Cognitive Assessment (MoCA) scale. Generalized Linear Models (GLM), Least absolute shrinkage and selection operator (Lasso) regression, Bayesian Kernel Machine Regression (BKMR), and Weighted Quantile Sum (WQS) were used to analyze the relationship between metal exposure, cognitive function, and the interaction with NLRP3 gene polymorphisms.

Results: Zinc (Zn) levels were positively associated with MoCA scores (β= 4.73, 95 % CI: 0.54, 8.92). A metal mixture (Na, Zn, Co, Mo, Ti, Sr, Ba) below the 60th percentile also showed a positive correlation with MoCA scores. The NLRP3 rs3806265C/C and rs4612666C/T and T/T genotypes were negatively associated with MoCA scores (β= -0.91, 95 % CI: -1.64, -0.17; β= -0.61, 95 % CI: -1.19, -0.02; β= -0.86, 95 % CI: -1.62, -0.10). In individuals with the C/T genotype of rs3806265 and rs4612666, Zn was positively associated with MoCA scores (β= 5.99, 95 % CI: 0.60, 11.38; β= 6.46, 95 % CI: 0.80, 12.12).

Conclusion: Decreased serum Zn levels may increase cognitive dysfunction risk. Individuals carrying the NLRP3 rs3806265C/C and rs4612666C/T or T/T more susceptible to cognitive decline. Individuals carrying the rs3806265C/T and rs4612666C/T genotypes are more likely to cause cognitive decline in the presence of Zn deficiency.

Keywords: Aluminum workers; Cognitive function; Gene polymorphisms; Metal levels; NLRP3.