A polymorphism in the delta-aminolevulinic acid dehydratase gene may modify the pharmacokinetics and toxicity of lead.

Abstract

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.Imagesp248-aFigure 1.

Children with moderately elevated blood lead levels: a role for other diagnostic tests?

“…Moderately elevated BPb levels indicate absorption of Pb, but do not necessarily predict the total amount of Pb accumulated in the body, the susceptibility of the individual child to a given amount of Pb, or the ability of chelating agents to enhance Pb excretion (22)(23)(24). Other diagnostic methods such as bone Pb measurements by X-ray fluorescence (XRF), EP level determinations, and the Pb-MT address some of these issues more directly (6,25,26).…”

Biomarkers of Lead Exposure.

“…T SAKAI Industrial Health 2000, 38, [127][128][129][130][131][132][133][134][135][136][137][138][139][140][141][142] The measurements or techniques in BM can be used for the diagnosis and also risk assessment of the toxic agents in the filed of environmental health, although BM should not be confused with diagnosis. The term, biological markers or biomarkers are general term for specific measurements reflecting an interaction between a biological system and an environmental agent, which may be chemical, physical, or biological 2) .…”

Genetic Susceptibility to Lead Poisoning

“…To determine whether ALAD polymorphism can influence lead excretion, Schwartz and co-workers (48) studied a group of Korean lead battery manufacturing workers with a mean blood lead concentration of 25 (49). In workers exposed to low levels of lead, subclinical kidney effects were more prominent in heterozygous individuals compared to ALAD1 homozygotes (44). The evidence summarized above suggests that the ALAD2 phenotype may enhance the detrimental effect on lead toxicity by affecting kidney function and decreasing the amounts of lead that are excreted after chelation.…”