Systemic review of genetic and epigenetic factors underlying differential toxicity to environmental lead (Pb) exposure

Lead (Pb) poisoning is a major public health concern in environmental justice communities of the USA and in many developing countries. There is no identified safety threshold for lead in blood, as low-level Pb exposures can lead to severe toxicity in highly susceptible individuals and late onset of diseases from early-life exposure. However, identifying “susceptibility genes” or “early exposure biomarkers” remains challenging in human populations. There is a considerable variation in susceptibility to harmful effects from Pb exposure in the general population, likely due to the complex interplay of genetic and/or epigenetic factors. This systematic review summarizes current state of knowledge on the role of genetic and epigenetic factors in determining individual susceptibility in response to environmental Pb exposure in humans and rodents. Although a number of common genetic and epigenetic factors have been identified, the reviewed studies, which link these factors to various adverse health outcomes following Pb exposure, have provided somewhat inconsistent evidence of main health effects. Acknowledging the compelling need for new approaches could guide us to better characterize individual responses, predict potential adverse outcomes, and identify accurate and usable biomarkers for Pb exposure to improve mitigation therapies to reduce future adverse health outcomes of Pb exposure.