The Association Between Serotonin Transporter Gene Promoter Polymorphism (5-HTTLPR), Self-Reported Symptoms, and Dental Mercury Exposure

Abstract

The associations between a polymorphism of the serotonin transporter gene (5-HTTLPR), dental mercury exposure, and self-reported symptoms were evaluated among 157 male dentists and 84 female dental assistants. Self-reported symptoms and detailed work histories were obtained by computerized questionnaire. Spot urine samples were collected and analyzed for mercury concentrations to evaluate recent exposures, whereas a chronic mercury exposure index was created from the work histories. 5-HTTLPR polymorphism status was determined using a polymerase chain reaction (PCR)-based assay. Scores for current, recent, and chronic self-reported symptom groups were evaluated with respect to recent and chronic mercury exposure and 5-HTTLPR polymorphism status. Multiple regression analysis controlled for age, socioeconomic status, tobacco and alcohol use, self-reported health problems, and medications. Analyses were restricted to Caucasian subjects due to the highly skewed distribution of the 5-HTTLPR polymorphism. Separate evaluations were conducted for dentists and dental assistants. In contrast to previous reports, no consistent associations were found between either urinary mercury concentration or the chronic index of mercury exposure and any category of symptoms. However, both significant and consistent associations were observed between increased symptoms and the 5-HTTLPR polymorphism involving two copies of the short or "s" allele (full mutation), but not with the polymorphism involving only one copy (heterozygous), demonstrating a gene-dose relationship for symptom reporting. These findings suggest that within this restricted population increased symptoms of depression, anxiety, and memory are associated with the 5-HTTLPR polymorphism among both males and females.Historically, occupational exposures to high levels of elemental mercury (Hg 0 ) have been associated with potentially severe neurological deficits (Albers et al., 1988;Langworth et al., 1992;Pranjic et al., 2003;Piikivi et al., 1984;Piikivi & Hanninen, 1989), whereas more recent studies reported such effects at substantially lower levels of Hg 0 exposure (Clarkson et al., 2003;Langworth et al., 1997;Ngim et al., 1992;Ritchie et al., 2002;Shapiro et al., 1982;Soleo et al., 1990). Our own studies documented adverse neurobehavioral effects associated with elemental mercury exposures in the range of those experienced by the general population with mercury amalgam dental fillings Echeverria et al., 1995Echeverria et al., , 1998. At such low levels of exposure, it becomes prudent to control for individual factors that may influence the sensitivity to Hg 0 -mediated effects. To this end, our previous studies described increased susceptibility to the adverse neurobehavioral effects of Hg 0 exposure among dentists and dental assistants expressing polymorphisms of genes encoding the heme biosynthetic pathway enzyme, coproporphyrinogen oxidase (CPOX) , and brain derived neurotrophic factor (BDNF) (Heyer et al., 2004;Echeverria et al., 2005). The polymorphism in e...

Genetic polymorphisms affecting susceptibility to mercury neurotoxicity in children: Summary findings from the Casa Pia Children's Amalgam Clinical Trial

“…Here, children who were genotyped with common variants of genes that have been previously shown to elicit no or only additive effects with Hg on neurobehavioral functions in adults, e.g., BDNF, CPOX, COMT, 5-HTTLPR (Echeverria et al, 2005, 2006, 2010; Heyer et al, 2004, 2008, 2009), displayed numerous significant interactive effects on comparable tests of neurobehavioral function at similar levels of Hg exposure. Since adverse neurobehavioral effects were found only among children having gene modifications, genexHg interactions are assumed to underlie these effects.…”

“…Such studies are relevant, however, in light of recent findings (Basu, et al, 2013; Echeverria et al, 2005, 2006, 2010; Goodrich et al, 2011; Gundacker et al, 2007, 2009; Heyer et al, 2004, 2008, 2009; Schläwicke Engstrom et al, 2008; Wang et al, 2012) identifying common variants of numerous genes that modify the effects of Hg on neurologic functions and/or Hg handling in human subjects. Identification of genetic polymorphisms that affect Hg neurotoxicity is of particular importance with regard to assessment of Hg risks in children, who may be uniquely susceptible, compared with adults, because of their smaller body mass and more rapidly developing, hence more fragile, nervous and metabolic systems (Landrigan and Goldman, 2011).…”

CatecholO-Methyltransferase (COMT)VAL158METFunctional Polymorphism, Dental Mercury Exposure, and Self-Reported Symptoms and Mood

“…As in our previous reports regarding studies with this dental professional cohort (Heyer et al, 2004, 2008; Woods et al, 2005; Echeverria et al, 2005, 2006), results for the (male) dentists and (female) dental assistants are analyzed and reported separately. This decision is based on the differences in the measures of Hg 0 exposure, age structures, education and training, and symptom reporting profiles for these two groups (Table 1).…”

“…In evaluating issues surrounding susceptibility to the neurological effects of Hg 0 at such low levels of exposure, it becomes necessary to take into account other biological causes for these effects, in particular, polymorphisms among genes that are known to influence the same neurobehavioral functions that are adversely impacted by Hg 0 exposure. In this regard, studies in an established cohort of occupationally exposed dental professionals have previously evaluated polymorphisms of genes influencing the production of coproporphyrinogen oxidase (CPOX)(Woods et al, 2005; Echeverria et al, 2006; Heyer et al, 2006), brain-derived neurotropic factor (BDNF) (Heyer et al, 2004; Echeverria et al, 2005), and the serotonin transporter gene promoter region (5-HTTLPR) (Heyer et al, 2008). CPOX was the first polymorphism studied, as it, along with Hg 0 , impacts the biosynthesis of heme, a likely mitigating factor in neurological signaling and neuronal functions (Chernova et al, 2007).…”

“…CPOX was the first polymorphism studied, as it, along with Hg 0 , impacts the biosynthesis of heme, a likely mitigating factor in neurological signaling and neuronal functions (Chernova et al, 2007). BDNF and 5-HTTLPR were similarly evaluated because of their known direct impact on mood and behavior (Heyer et al, 2004, 2008). Independent and additive, although not interactive (i.e., synergistic), effects were associated with Hg 0 and each of these polymorphisms.…”