Effect of interaction of ATG7 and plasma heavy metal on cognitive impairment in rural China

Abstract Objective To analyze the relationship between the concentration of heavy metals in plasma and the occurrence of cognitive dysfunction using multiple models. Methods A cross-sectional survey was conducted in rural China among 961 individuals aged 50 years or older. Cognitive function was assessed using the Mini-Mental State Examination (MMSE). Genetic analysis focused on two single nucleotide polymorphisms (SNPs) in the autophagy-related gene ATG7 (rs2606757 and rs8154). Plasma concentrations of heavy metals were quantified using inductively coupled plasma mass spectrometry. Restricted cubic splines were used to explore the association between serum metal concentration and the occurrence of mild cognitive impairment in populations of various genotypes. Bayesian Kernel Machine Regression(BKMR) models were used to explore the interactions between individual metals. Results In a restricted cubic spline model, there is a nonlinear relationship between plasma concentration of Cd and the occurrence of cognitive impairment in populations carrying the population carrying AA(P of Nonlinear = 0.036) and AT( P of Nonlinear = 0.027) genotypes at the rs2606757. However, in people carrying the TT genotype at the rs2606757 locus, the concentration of heavy metals in plasma was not significantly associated with the occurrence of cognitive impairment. The results of the BKMR model are consistent with those of the restricted cubic spline. Conclusion The TT genotype at rs2606757 in ATG7 appears to confer greater cognitive resilience against heavy metal-induced damage. These findings highlight the importance of considering gene-environment interactions in the context of cognitive impairment and suggest potential avenues for preventing cognitive decline in populations exposed to heavy metals. Further research is needed to elucidate the precise mechanisms underlying these interactions.