## 4 Discussion
Studies conducted by the United Nations on gold-working artisans in the Philippines, Indonesia, Tanzania, and Zimbabwe point in the right direction and should be followed by interventions to improve the conditions of these workers. Unfortunately, the increase in occupational exposure to mercury, as recorded throughout the world, principally involves developing countries or those in which industrial development takes place without due regard for Western health and safety standards. In such countries, the clinical and genetic evaluation of workers is undoubtedly difficult, as is demonstrated in Siberia where even the type of work activity is unknown. The difficulty of being able to study an occupational cohort exposed to significant levels of mercury vapor, added to the complexity, invasiveness and cost of the tests required have limited research. Dental workers, who were willing to undergo the complex analyses needed to identify pre-clinical alterations, have gradually adopted measures to reduce their occupational exposure. Dental exposure to mercury has fallen significantly over the last few decades. Consequently, mean urinary mercury concentrations in dentists are currently approaching levels observed in the general population. The difference between the positive findings of the Washington cohort, recruited in 1999, and the negative results in the more recent Michigan sample, indicates the current difficulty in obtaining a sample of high-dose exposed and available workers in Western countries. Previous studies in non-occupational settings have provided sufficient evidence of the role of SNPs in Hg toxicity. These studies, however, focus mainly on organic mercury that has a different toxicological profile from that of the elemental metal. For example, maternal polymorphisms in glutathione-related genes were associated with maternal mercury concentrations and early child neurodevelop in a population with a fish-rich diet [60]. Genetic polymorphisms of catechol-O-methyltransferase were found to modify the neurobehavioral effects of mercury in children [61], and an increased susceptibility to the adverse neurobehavioral effects of Hg was found among children with relatively common genetic variants of metallothionein [62]. While levels of mercury exposure have fallen in industries (at least in developed countries), the accumulation of Hg in biota and its biomagnification in aquatic food chains pose a real threat to public health [63; 64]. Recent studies have shown that increasing concentrations of inorganic Hg may be present in the brain of relatively low exposure subjects as they get older, and that the pattern of Hg deposition in the brain tissues of individuals exposed to environmental pollution is different from that of workers with acute or subacute exposures to lethal or significantly higher concentrations in workplaces [65]. The spread of this neurotoxic metal in the environment and its bioaccumulation in the food chain are leading to epigenetic consequences [66]. Other neurotoxic metals, such as aluminum, may be present in the environment [67], and this can definitively increase the risk for occupationally exposed workers. Future occupational studies will need to take these important factors into account. The limitations of our review are clearly related to some aspects of the occupational studies: observations are derived from only three research groups; they are only cross-sectional, conducted on small groups and do not take into account all the numerous confounding factors and possible impact of linkage disequilibrium. The presence of these limitations is also the main merit of the work done since it underlines the need for further research into the gene-environment interaction in a sector of great interest for public health.