Ecogenetics of mercury: From genetic polymorphisms and epigenetics to risk assessment and decision‐making

Abstract

The risk assessment of mercury (Hg), in both humans and wildlife, is made challenging by great variability in exposure and health effects. Although disease risk arises following complex interactions between genetic ("nature") and environmental ("nurture") factors, most Hg studies thus far have focused solely on environmental factors. In recent years, ecogenetic-based studies have emerged and have started to document genetic and epigenetic factors that may indeed influence the toxicokinetics or toxicodynamics of Hg. The present study reviews these studies and discusses their utility in terms of Hg risk assessment, management, and policy and offers perspectives on fruitful areas for future research. In brief, epidemiological studies on populations exposed to inorganic Hg (e.g., dentists and miners) or methylmercury (e.g., fish consumers) are showing that polymorphisms in a number of environmentally responsive genes can explain variations in Hg biomarker values and health outcomes. Studies on mammals (wildlife, humans, rodents) are showing Hg exposures to be related to epigenetic marks such as DNA methylation. Such findings are beginning to increase understanding of the mechanisms of action of Hg, and in doing so they may help identify candidate biomarkers and pinpoint susceptible groups or life stages. Furthermore, they may help refine uncertainty factors and thus lead to more accurate risk assessments and improved decision-making.

Benefits of mercury controls for the United States

“…Although convincing evidence is present to associate MeHg with adverse human effects at low to medium doses, particularly for IQ deficits (7,50), there may be variability in the magnitude of this effect; for instance, because of genetic variability (51). As a result, we use 95% confidence interval bounds for high and low cases for biomarker and dose-response parameters (SI Appendix, Table S3).…”

Epigenetics of oral infection and inflammatory diseases—DNA methylation changes in infections and inflammation diseases

“…As previously mentioned, DNA methylation by hepatitis C, Epstein-Barr virus, human papilloma viruses, and H. pylori may be associated with the development lichen planus [22,23]. Amalgam restoration is also related to the etiology of lichen planus [49], because mercury may cause aberrant DNA methylation [50]. Increased expression of DNMT may induce lichen planus via the hypermethylation of some genes by microbial infections, however further investigation is needed.…”

Consensus document on the prevention of methylmercury exposure in Spain

“…Studies performed in recent years have begun to document genetic and epigenetic factors that can influence the toxicokinetics of mercury and modify individual health risks associated with exposure, which would explain part of the variability in susceptibility to mercury toxicity [38,39].…”