A polymorphism in the delta-aminolevulinic acid dehydratase gene may modify the pharmacokinetics and toxicity of lead.
Associations between the presence of a constitutional variant of delta-aminolevulinic acid dehydratase (ALAD-2) and lead concentrations in blood and bone, as well as between this allele and indices of kidney function, were investigated among 691 members of a construction trade union. The average blood lead level in this group was 7.78 micrograms/dl. No significant difference was observed in blood lead concentration in ALAD-2 carriers compared to those homozygous for the more common ALAD-1 allele (7.78 +/- 3.62 micrograms Pb/dl vs. 7.73 ( +/- 3.48 micrograms Pb/dl, respectively; p = 0.73). Bone lead was measured in a subset of 122 of the study subjects. Patella minus tibia lead concentrations for each individual averaged 3.35 +/- 11.99 micrograms Pb/g bone mineral in ALAD-1 homozygotes and 8.62 +/- 9.47 micrograms Pb/g bone mineral in ALAD-2 carriers (p = 0.06). Comparisons of blood urea nitrogen (BUN) and uric acid by genotype indicated elevated levels among ALAD-2 individuals (p = 0.03 and 0.07, respectively). In logistic regression models accounting for other variables potentially associated with BUN and uric acid levels, BUN was significantly associated with blood lead levels (p = 0.01). Associations of BUN and uric acid levels with ALAD-2 were of borderline statistical significance in these models (p = 0.06 and 0.07). Taken together, these results suggest that the ALAD-2 genotype may influence the pharmacokinetic distribution and chronic renal toxicity of lead, perhaps due to differential binding of lead to the variant protein.
Smith
C M
CM
Department of Cancer Biology, Harvard School of Public Health, Boston, MA 02115, USA.
Wang
X
X
Hu
H
H
Kelsey
K T
KT
D000328:Adult; D000483:Alleles; D001483:Base Sequence; D001806:Blood Urea Nitrogen; D001842:Bone and Bones / Q000737:chemistry; D003252:Construction Materials; D006579:Heterozygote; D006720:Homozygote; D006801:Humans; D007854:Lead / Q000032:analysis* / Q000097:blood / Q000493:pharmacokinetics; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D016273:Occupational Exposure; D016133:Polymerase Chain Reaction; D000623:Porphobilinogen Synthase / Q000235:genetics*
D007854:Lead; D000623:Porphobilinogen Synthase