Genetic Susceptibility as Potential Modifier of Health Risks from Exposure to Toxic Elements

Genetic variability is increasingly recognized as a key determinant of individual susceptibility to heavy metal-induced toxicity. Beyond exposure intensity and duration, inherited differences in genes regulating metal transport, detoxification, and DNA repair can substantially influence internal dose and biological response. To date, research has primarily focused on variants within these pathways, particularly single-nucleotide polymorphisms (SNPs), some of which have been proposed as potential susceptibility markers for toxic element (TE) toxicity. Despite these advances, current findings remain inconsistent. Many studies are limited by small sample sizes, heterogeneous exposure assessment, and insufficient consideration of ethnic-specific allelic diversity and gene-environment interactions. Future research should prioritize large, well-characterized, and ethnically diverse populations, integrating detailed exposure profiling, lifestyle factors, and co-exposures to more accurately define the genetic architecture underlying susceptibility. Therefore, in this review, we summarize the principal toxic metals, synthesize epidemiological evidence linking exposure to adverse health outcomes, and explore the contribution of genetic variability in modulating individual risk of metal-induced disease.