Author: Woods JS, Heyer NJ, Russo JE, Martin MD, Pillai PB, Bammler TK, Farin FM.
Source: Journal of Toxicology and Environmental Health
Year: 2014
Comment:
The researchers of this study on dental amalgam fillings in children state, "In conclusion, the present studies demonstrate significant adverse effects of a relatively common genetic variant of COMT rs4680, either individually or within haplotype configuration, on neurobehavioral functions associated with Hg exposure among children, principally boys. These findings extend previous observations describing altered genetic susceptibility to the adverse neurobehavioral effects of Hg exposure in children, and may have important public health implications for future strategies aimed at protecting children and adolescents from the potential health risks associated with Hg exposure."
Abstract / Excerpt:
“Mercury (Hg) is neurotoxic and children may be particularly susceptible to this effect. A current major challenge is identification of children who may be uniquely susceptible to Hg toxicity because of genetic disposition. This study examined the hypothesis that genetic variants of catechol-O-methyltransferase (COMT) that are reported to alter neurobehavioral functions that are also affected by Hg in adults might modify the adverse neurobehavioral effects of Hg exposure in children. Five hundred and seven children, 8–12 yr of age at baseline, participated in a clinical trial to evaluate the neurobehavioral effects of Hg from dental amalgam tooth fillings. Subjects were evaluated at baseline and at seven subsequent annual intervals for neurobehavioral performance and urinary Hg levels. Following the clinical trial, genotyping assays were performed for single-nucleotide polymorphisms (SNPs) of COMT rs4680, rs4633, rs4818, and rs6269 on biological samples provided by 330 of the trial participants. Regression-modeling strategies were employed to evaluate associations between allelic status, Hg exposure, and neurobehavioral test outcomes. Similar analysis was performed using haplotypes of COMT SNPs. Among girls, few interactions for Hg exposure and COMT variants were found. In contrast, among boys, numerous gene–Hg interactions were observed between individual COMT SNPs, as well as with a common COMT haplotype affecting multiple domains of neurobehavioral function. These findings suggest increased susceptibility to the adverse neurobehavioral effects of Hg among children with common genetic variants of COMT, and may have important implications for strategies aimed at protecting children from the potential health risks associated with Hg exposure.”
Citation:
Woods JS, Heyer NJ, Russo JE, Martin MD, Pillai PB, Bammler TK, Farin FM. Genetic polymorphisms of catechol-O-methyltransferase modify the neurobehavioral effects of mercury in children. Journal of Toxicology and Environmental Health. 2014; Part A, 77(6): 293-312.