Genetic polymorphisms and mechanisms of neurotoxicity: overview.

Genetic polymorphisms may affect the susceptibility of individuals or populations to toxic agents that cause developmental defects or disease. This commentary outlines basic concepts of genetic polymorphisms and their relevance to environmentally-induced diseases. First, we provide a basic overview of genetic polymorphisms, with emphasis on single nucleotide polymorphisms (SNPs). Next, we summarize the approach of the NIEHS-sponsored Environmental Genome Project, which focuses on SNPs as an efficacious approach to understand gene–environmental interactions. Genes that have possible relevance to neurotoxicity are presented in a table with annotations regarding their known interactions with neurotoxicants. Research on three of these genes, d-aminolevulinic acid dehydratase (ALAD), human serum paraoxonase (PON1), and monoamine oxidase B (MAO-B) is briefly reviewed. We also comment on the high number of genes and gene products in the nervous system that increase the complexity of the search for environmentally relevant genes in neurotoxicity. Finally, we list several prospects for further research.