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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.

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  • Authors+Show Affiliations

    ,

    Department of Cancer Biology, Harvard School of Public Health, Boston, MA 02115, USA.

    , ,

    Source

    Environmental health perspectives 103:3 1995 Mar pg 248-53

    MeSH

    Adult
    Alleles
    Base Sequence
    Blood Urea Nitrogen
    Bone and Bones
    Construction Materials
    Heterozygote
    Homozygote
    Humans
    Lead
    Male
    Middle Aged
    Molecular Sequence Data
    Occupational Exposure
    Polymerase Chain Reaction
    Porphobilinogen Synthase

    Pub Type(s)

    Journal Article
    Research Support, Non-U.S. Gov't
    Research Support, U.S. Gov't, P.H.S.

    Language

    eng

    PubMed ID

    7768225

    Citation

    Smith, C M., et al. "A Polymorphism in the Delta-aminolevulinic Acid Dehydratase Gene May Modify the Pharmacokinetics and Toxicity of Lead." Environmental Health Perspectives, vol. 103, no. 3, 1995, pp. 248-53.
    Smith CM, Wang X, Hu H, et al. A polymorphism in the delta-aminolevulinic acid dehydratase gene may modify the pharmacokinetics and toxicity of lead. Environ Health Perspect. 1995;103(3):248-53.
    Smith, C. M., Wang, X., Hu, H., & Kelsey, K. T. (1995). A polymorphism in the delta-aminolevulinic acid dehydratase gene may modify the pharmacokinetics and toxicity of lead. Environmental Health Perspectives, 103(3), pp. 248-53.
    Smith CM, et al. A Polymorphism in the Delta-aminolevulinic Acid Dehydratase Gene May Modify the Pharmacokinetics and Toxicity of Lead. Environ Health Perspect. 1995;103(3):248-53. PubMed PMID: 7768225.
    * Article titles in AMA citation format should be in sentence-case
    TY - JOUR T1 - A polymorphism in the delta-aminolevulinic acid dehydratase gene may modify the pharmacokinetics and toxicity of lead. AU - Smith,C M, AU - Wang,X, AU - Hu,H, AU - Kelsey,K T, PY - 1995/3/1/pubmed PY - 1995/3/1/medline PY - 1995/3/1/entrez SP - 248 EP - 53 JF - Environmental health perspectives JO - Environ. Health Perspect. VL - 103 IS - 3 N2 - 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. SN - 0091-6765 UR - https://www.unboundmedicine.com/medline/citation/7768225/A_polymorphism_in_the_delta_aminolevulinic_acid_dehydratase_gene_may_modify_the_pharmacokinetics_and_toxicity_of_lead_ L2 - https://ehp.niehs.nih.gov/doi/full/10.1289/ehp.95103248?url_ver=Z39.88-2003&rfr_id=ori:rid:crossref.org&rfr_dat=cr_pub=pubmed DB - PRIME DP - Unbound Medicine ER -