Ecogenetics of lead toxicity and its influence on risk assessment

Lead (Pb) toxicity is a public health problem affecting millions worldwide. Advances in 'omic' technology have paved the way to toxico-genomics which is currently revolutionizing the understanding of interindividual variations in susceptibility to Pb toxicity and its functional consequences to exposure. Our objective was to identify, comprehensively analyze, and curate all the potential genetic and epigenetic biomarkers studied to date in relation to Pb toxicity and its association with diseases. We screened a volume of research articles that focused on Pb toxicity and its association with genetic and epigenetic signatures in the perspective of occupational and environmental Pb exposure. Due to wide variations in population size, ethnicity, age-groups, and source of exposure in different studies, researchers continue to be skeptical on the topic of the influence of genetic variations in Pb toxicity. However, surface knowledge of the underlying genetic factors will aid in elucidating the mechanism of action of Pb. Moreover, in recent years, the application of epigenetics in Pb toxicity has become a promising area in toxicology to understand the influence of epigenetic mechanisms such as DNA methylation, chromatin remodeling, and small RNAs for the regulation of genes in response to Pb exposure during early life. Growing evidences of ecogenetic understanding (both genetic and epigenetic processes) in a dose-dependent manner may help uncover the mechanism of action of Pb and in the identification of susceptible groups. Such studies will further help in refining uncertainty factors and in addressing risk assessment of Pb poisoning.