## 3 Results
#### Study Selection and Characteristics  
All studies had a cross-sectional design. The quality of studies was mainly moderate to low (ranging from 2 to 7 on the 10-point NOS-A scale). The studies were conducted mainly in the USA; one study was performed by the Global Mercury Project (GMP) implemented by the United Nations Industrial Development Organization (UNIDO) in developing countries, one in Ecuador, and one study was carried out in Russia. Six of the 7 American studies were conducted on the same cohort of dental workers, selected between 1998 and 2001 and composed of 193 male dentists and 230 female dental assistants belonging to the Washington State Dental Association with an average of 18 years of Hg-related exposure. The participants in the other American study were recruited during the Michigan Dental Association (MDA) annual conventions held in 2009 (n = 232) and 2010 (n = 283). The Russian study was performed on 116 men chronically exposed to metallic Hg in 2005-2006 and 2009-2010. The UNIDO studies were based on 558 Hg-exposed workers in Asia and Africa. The Ecuadorian study recruited 200 miners and 37 gold merchants. Quantitative meta-analytical analyzes could not be performed due to the modest size of the case series, the overlapping of observations, and the use of a number of confounding. The studies included in our review examined some Hg neurotoxicity mechanisms in order to identify genetic variations related to neurotoxicity. Different genes were taken into consideration. To date, no study has checked the results of previous studies. The studies we examined did not consider the bio-metabolism of mercury and the genes that can influence its absorption, distribution, or excretion. They focused on variations that can favour some neurotoxic effects of the metal. Their aim was to detect individual factors that may influence sensitivity to Hg-mediated effects, due to polymorphisms within genes that are known to influence the same neurobehavioral functions that are adversely impacted by Hg exposure. US studies on the Washington cohort focused on early neurobehavioral effects (mood and symptoms) associated with elemental mercury exposures among dental practitioners. A weighted chronic mercury exposure index was created for participants by adding together the contribution of each of their reported dental-related jobs, and a weighting factor based on the time-period of the job. An acute cumulative mercury exposure index based on urinary mercury was also calculated. Subjects underwent neuropsychological testing and reported symptoms. The studies investigated single nucleotide polymorphisms (SNPs) of some genes that code for proteins essential for the central nervous system. The first target studied was the Brain-Derived Neurotrophic Factor (BDNF), a protein that regulates neuronal growth and differentiation in the peripheral and central nervous system [37], whose secretion and processing can be altered by an SNP (G196A) leading to the substitution of valine (val) with methionine (met) in the BDNF gene at codon 66 (val66 met). In measurement of memory, the BDNF polymorphism has been linked to abnormal hippocampal activation and reduced performance [38; 39; 40]. Neurological effects in US workers exposed to Hg were associated with BDNF status, with a joint additive effect of Hg exposure and BDNF polymorphism reported for some neurological measurements. The results obtained in these dental workers in relation to mood and symptoms in 2004 [41] were confirmed the following year in a slightly increased number of cases regarding the effect on cognitive and motor performance scores [42]. Subsequently, the same research group described an SNP (A814C) in exon 4 resulting in an aspargin to histidine substitution at codon 272 (asn272 his) of the gene encoding the heme biosynthetic pathway enzyme, coproproproyrinogen oxidase (CPOX), which significantly modifies the effect of Hg exposure on urinary porphyrin excretion in humans.