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Final Progress Reports: University of Washington: Heme Pathway Polymorphisms in Mercury Neurotoxicity in Adults and Children

Superfund Research Program

Heme Pathway Polymorphisms in Mercury Neurotoxicity in Adults and Children

Project Leader: James S. Woods
Grant Number: P42ES004696
Funding Period: 1995 - 2009
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Final Progress Reports

Year:   2008  2005  1999 

Dr. Woods and his team of researchers confirmed that a previously identified polymorphism in the human coproporphyrinogen oxidase (CPOX) gene modifies effect of mercury exposure on a number of neurobehavioral functions, including attention span, motor function and visual memory.  These finding establish, for the first time, a possible genetic predisposition to altered susceptibility to mercury toxicity in humans.  In related studies, project researchers described a novel computational approach to risk assessment using cascade analysis of the interaction of mercury and CPOX polymorphism on porphyrin production to characterize complex metabolic responses and interactions associated with toxicant exposure and genetic variation in humans.

In additional studies, the researchers performed preliminary genotyping assays for the 5-HTTLPR-S polymorphism in the current study population of dental professionals with long-term occupational mercury exposure. This polymorphism in the serotonin (5-HT) transporter is associated with depressive symptoms, behavioral disorders and excessive shyness, similar to symptoms of prolonged mercury exposure (“mad hatter syndrome”). Genotypes were distributed according to the Hardy-Weinberg equilibrium: 31% +/+, 51% +/-, 18% -/-, attesting to the widespread prevalence of the polymorphisms in this population.  Continuing studies will determine if 5-HTTLPR-S modifies the effect of mercury exposure neurobehavioral parameters in both adults and children.

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