A polymorphism in the delta-aminolevulinic acid dehydratase gene may modify the pharmacokinetics and toxicity of lead.
Smith-CM; Wang-X; Hu-H; Kelsey-KT
Environ Health Perspect 1995 Mar; 103(3):248-253
A group of 691 members of a construction trade union was studied to determine possible alterations in lead (7439921) kinetics associated with delta-aminolevulinic-acid-dehydratase (ALAD) genotype. In the entire group the average blood lead level was 7.78 micrograms/deciliter (microg/dl). There was no difference found in the blood lead levels in ALAD-2 carriers compared to those homozygous for the ALAD-1 allele. K-XFR was used to determine bone lead; determinations were made in 122 of the subjects. For each of these individuals the patella minus tibia lead concentration averaged 3.35+/-11.99 micrograms of lead/gram (microg/g) of bone material in ALAD-1 homozygotes and 8.62+/-9.47microg/g in ALAD-2 carriers. Elevated levels of blood urea nitrogen (BUN) and uric- acid were detected among ALAD-2 carriers. There was a borderline association of BUN and uric-acid levels with ALAD-2. The authors conclude that the pharmacokinetic distribution and chronic renal toxicity of lead may be influenced by the ALAD-2 genotype. They suggest that this influence may arise through the differential binding of lead to the variant protein.
NIOSH-Publication; NIOSH-Grant; Cancer; Lead-poisoning; Construction-workers; Genetic-factors; Lead-compounds; Blood-analysis; Biological-monitoring; Enzyme-activity; Humans
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Environmental Health Perspectives
Harvard University, Boston, Massachusetts