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Harvard School of Public Health

Superfund Research Program

Genetic Susceptibility to Environmental Lead Intoxication

Project Leader: Karl T. Kelsey
Grant Number: P42ES005947
Funding Period: 1995 - 2006
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Project Summary (1995-2000)

This project's research aim is to identify and validate biomarkers that may improve the effectiveness of screening and clinical treatment efforts for lead poisoning. A common genetic polymorphism in aminolevulinate dehydratase (ALAD) has been associated with elevated blood-lead levels in children and adults. This may be due to a greater affinity of the variant ALAD-2 enzyme for lead binding. It is hypothesized that ALAD genotype will provide a useful biomarker of the effectiveness of chelation therapy used in the treatment of lead poisoning. It is also hypothesized that the ALAD-2 enzyme will be protective of lead toxicity by sequestering lead from sensitive sites of neurotoxic action. Additional work includes the ongoing examination of the possible association of the ALAD gene variant and maternal and offspring blood lead levels. These issues are being studied in a population in Korea. Environmental exposure to lead is higher in Korea than in the United States, thus the study can be done with fewer subjects. Also, collaboration with an ongoing study has enabled rapid start-up and efficient collection of data.

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