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University of Washington

Superfund Research Program

Heme Pathway Polymorphisms in Mercury-Induced Porphyrinuria and Toxicity

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

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Project Summary (2000-2006)

The objective of this project is to define the association between the genetic polymorphisms of two heme biosynthetic pathway enzymes, uroporphyrinogen decarboxylase (UROD) and coproporphyrinogen oxidase (CPOX), and the atypical porphyrinogenic response to mercury (Hg) exposure in human subjects. The long-term goal is to establish a biomarker based on a genetically-linked effect of Hg on porphyrinmetabolism and the urinary porphyrin profile. This biomarker could identify persons who are at increased risk of Hg toxicity during low-level environmental Hg exposure. Researchers are using novel and established genetic analytical techniques, along with validated neurobehavioral and clinical testing procedures, in an established, well-characterized and highly motivated human population. This population has experienced low-level Hg exposure comparable to that of people residing near Superfund hazardous waste sites. The finding of a significant relationship between specific polymorphisms in the UROD and/or CPOX genes and the atypical porphyrinogenic response to Hg would represent the first such discovery of a genetic predisposition to an altered biological response to Hg that could be reflected in altered Hg disposition and associated health risks in human subjects.

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