## 3 Results
#### Study Selection and Characteristics
Indeed, this polymorphism exacerbates an abnormal urinary porphyrin excretion pattern associated with mercury exposure [43]. Hence, they examined the neurobehavioral consequences of this polymorphism (\"CPOX4\") in dental professionals, showing a limited effect on neurobehavioral performance, attention and mood, that is independent (not interactive) and additive with Hg exposure on visuomotor performance [44]. This means that, when occurring simultaneously, Hg exposure and the presence of the polymorphism increased the overall adverse outcome. Another aspect of mercury neurotoxicityology that has been investigated is the uptake of serotonin. An insertion/deletion polymorphism in the polymorphic region of the serotonin transporter (5-HTT) gene (SLC6A4) located on chromosome 17q11, termed serotonin transporter gene-linked polymorphic region (5-HTTLPR), has the potential to regulate the level of the functional serotonin transporter. Compared to the long (\"1\") allele (wild-type), the short allele (\"s\" polymorphism) has been found to halve serotonin uptake [45], and this has been associated with the presence of anxiety, depression, affective states, and other mental health problems in humans [46; 47]. In a preliminary study, the analysis of data from a subsample of the Washington cohort of dental workers showed that 5-HTTLPR polymorphism with full mutation (ss) was associated with increased self-reported symptoms of depression, anxiety and memory, but no significant interactions between Hg exposure and the 5-HTTLPR polymorphism were found [48]. In a subsequent study, exposure to Hg and the presence of the 5-HTTLPR polymorphism independently altered behavioral performance and mood state [49]. Some neurobehavioral domains were additively affected by both Hg exposure and the genetic variant. A transcriptional substitution of methionine for valine at codon 158 of the gene encoding for Catechol O-methyltransferaseerase (COMT), an important enzyme in the methylation of endogenous and exogenous catechol compounds, including catecholamine neurotransmitters and estrogens, results in decreased enzymatic activity compared with the wild-type allele of the gene, and has been related with changes in cognitive function and affective responses (REF). In the Washington cohort, several types of symptoms were associated with both Hg exposure and COMT polymorphism, especially full mutation (two Met158 alleles) suggesting a gene-dose effect [50]. Another US study was performed on a sample of 515 dental workers (dentists, dental hygiists, and dental assistants) of the Michigan Dental Association, recruited in 2009 and 2010. Subjects provided urine and hair samples for Hg measurement, performed measurement of sensory nerve conduction, and completed a hand symptom diagram for carpal tunnel syndrome. Genotyping for 15 SNPs from selenoprotein and glutathione-related genes along with 13 metallothioneen SNPs was performed. Most of these polymorphisms had been previously reported [51] or hypothesized to significantly modify Hg effects in humans, since they were related to genes involved in Hg metabolism or functioning as antioxidants. The complex set of relationships investigated led to the creation of 504 multivariate linear regression models predicting nerve function, of which only 3 indicated a significant SNP-Hg level interaction, specifically for glutathione peroxidase 1 (GPX1), metallothioneen 1E (MT1E), and glutamate cysteine ligase catalytic subunit (GCLC). The authors concluded that there was little evidence that the SNPs studied modified the effect of the relationship between nerve function and mercury burden in the body [52]. The Russian study was conducted in Siberia on 116 men recruited in two phases (2005-2006 and 2009-2010), all of whom had been exposed to mercury for a long period (>10 years) and most of whom were affected by current or past chronic Hg intoxication. Cytochrome P450-dependent monooxygenase (CYP) activity plays a key role in the metabolism of xenobiotic and endogenous substrates.