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Genetic Polymorphisms of Catechol-O-Methyltransferase Modify the Neurobehavioral Effects of Mercury in Children

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Title Genetic Polymorphisms of Catechol-O-Methyltransferase Modify the Neurobehavioral Effects of Mercury in Children
 
Creator WOODS, JS
HEYER, NJ
RUSSO, JE
MARTIN, MD
PILLAI, PB
BAMMLER, TK
FARIN, FM
 
Subject RANDOMIZED CLINICAL-TRIAL
PREFRONTAL CORTEX
FUNCTIONAL POLYMORPHISM
COPROPORPHYRINOGEN OXIDASE
METHYLMERCURY EXPOSURE
COGNITIVE FUNCTION
SEX-DIFFERENCES
DENTAL AMALGAM
MESSENGER-RNA
COMT
 
Description 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.
 
Publisher TAYLOR & FRANCIS INC
 
Date 2014-12-28T10:52:19Z
2014-12-28T10:52:19Z
2014
 
Type Article
 
Identifier JOURNAL OF TOXICOLOGY AND ENVIRONMENTAL HEALTH-PART A-CURRENT ISSUES, 77(6)293-312
1528-7394
1087-2620
http://dx.doi.org/10.1080/15287394.2014.867210
http://dspace.library.iitb.ac.in/jspui/handle/100/16287
 
Language English