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

Abstract

Associations were evaluated between a functional single nucleotide polymorphism (Val158Met) in the gene encoding the catecholamine catabolic enzyme catechol O-methyltransferase (COMT), dental mercury exposure, and self-reported symptoms and mood among 183 male dentists and 213 female dental assistants. Self-reported symptoms, mood, 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 for all subjects was created from the work histories. COMT polymorphism status was determined using a polymerase chain reaction (PCR)-based assay. Scores for current, recent, and chronic self-reported symptom groups and six self-reported mood factors were evaluated with respect to recent and chronic mercury exposure and COMT polymorphism status. Multiple regression analysis controlled for age, socioeconomic status, tobacco and alcohol use, self-reported health problems, and medications. Separate evaluations were conducted for dentists and dental assistants. No consistent patterns of association between either urinary mercury concentration or the chronic index of mercury exposure and any category of symptoms were observed. However, consistent and significant associations were found between increased symptoms and the COMT polymorphism involving the double allelic substitution (full mutation) compared to subjects with no substitutions. Associations with mood were limited to polymorphism status among female dental assistants, and were observed for four of six mood factors and overall mood score. These findings extend evidence of genetic factors potentially affecting human susceptibility to the toxic effects of mercury and other environmental chemicals.Potentially severe neurological deficits have historically been associated with occupational exposures to high levels of elemental mercury (Hg 0 ) (Albers et al., 1988;Langworth et al., 1992;Piikivi et al., 1984;Piikivi & Hanninen, 1989). More recent studies of lower levels of Address correspondence to James S. Woods, PhD, Department of Environmental and Occupational Health Sciences, University of Washington, 4225 Roosevelt Way NE, Suite 100, Seattle, WA 98105, USA. jwoods@u.washington.edu. Publisher's Disclaimer: Full terms and conditions of use: http://www.informaworld.com/terms-and-conditions-of-access.pdf This article may be used for research, teaching and private study purposes. Any substantial or systematic reproduction, re-distribution, re-selling, loan or sub-licensing, systematic supply or distribution in any form to anyone is expressly forbidden. The publisher does not give any warranty express or implied or make any representation that the contents will be complete or accurate or up to date. The accuracy of any instructions, formulae and drug doses should be independently verified with primary sources. The publisher shall not be liable for any loss, actions, claims, proceedings, demand or costs or damages wha...

Evaluation of GlutathioneS-transferaseGSTM1andGSTT1Polymorphisms and Methylmercury Metabolism in an Exposed Amazon Population

“…Several GSH-related enzymes are highly polymorphic, and epidemiological studies demonstrated that these polymorphisms may affect the metabolism of Hg (Goyer and Clarkson 2001;Gundacker et al 2010). Moreover, other studies were carried out concerning the relationship between other polymorphisms and adverse health effects induced by Hg exposure (de Marco et al 2011;Echeverria et al 2010;Heyer et al 2009). The GST genes, especially GSTM1 (mu) and T1 (theta), are important since they present a deletion that results in impaired catalytic activity associated with greater sensitivity to toxic compounds.…”

Influence of Val108/158Met COMT Gene Polymorphism on the Efficacy of Modified Electroconvulsive Therapy in Patients with Treatment Resistant Depression

“…In this study, MECT treatment produced a significant effect on the scores of total and individual factors of the HAMD, a scale that is indicative of depression and a guide to assess recovery. Catechol O-methyltransferase (COMT) is the main enzyme involved in the catabolism of endogenous catecholamine such as adrenaline, noradrenaline, and dopamine [20,22,23,25]. The role of COMT in the occurrence and development of various neuropsychiatric disorders such as migraine, Parkinson's syndrome, and schizophrenia has been recognized [8,19].…”

“…Individuals with double allelic substitution in the COMT gene have been shown to exhibit increased mood symptoms compared to those with no substitution [23].…”

“…As a result of this substitution of the Met, COMT is expressed as a soluble (S.COMT) enzyme, whereas a substitution of 158th Val with Met transcribes the membrane-bound (MB.COMT) protein [21]. The wild-type gene Val/Val (G/ G) produces highly active COMT, whereas the mutated variants, Va1/Met (A/G) and Met/Met (A/A) generate enzymes of moderate and low activity, respectively [22][23][24]. The schizophrenia patients with Va1/Va1 (G/G) have been found to exhibit higher sensitivity to the MECT treatment than those with other two genotypes of COMT implying a correlation between the gene type and depressive disorder [25].…”

Further Thoughts on Mercury, Epigenetics, Genetics and Amyotrophic Lateral Sclerosis

“…Moving away from epigenetic considerations, Callaghan et al [1] [4][5][6][7] . Using neurobehavioural testing, low-level mercury exposure was seen to be independently significantly associated with deficits in manual coordination skills [4] .…”