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Background  The aim was to examine the link between low-level arsenic exposure and cognitive functioning, and the potential role of a single nucleotide polymorphism (SNP A35991G, rs10748835) of the AS3MT gene in modifying this link.    Methods  Data were analyzed on 526 participants from Project FRONTIER. Hierarchical linear regressions were created with neuropsychological raw index scores as the outcome variable and arsenic exposure and AS3MT SNP as different predictor variables.    Results  Within the total sample, arsenic exposure was negatively associated with language (p < 0.001) and executive functioning (p < 0.001). Among those with the AA genotype of the AS3MT gene, arsenic levels were negatively associated with language (p < 0.001), attention (p = 0.01), and executive functioning (p = 0.04). Among those with the AG genotype, arsenic levels were positively associated with immediate (p = 0.04) and delayed memory (p < 0.001) and negatively associated with executive functioning (p = 0.03). Among those with the GG genotype, arsenic levels were negatively associated with visuospatial functioning (p = 0.02).    Conclusions  Low-level arsenic exposure is associated with cognitive functioning; however, this association is modified by an AS3MT gene.

Arsenic exposure, AS3MT polymorphism, and neuropsychological functioning among rural dwelling adults and elders: a cross-sectional study