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Associations of blood lead, dimercaptosuccinic acid-chelatable lead, and tibia lead with polymorphisms in the vitamin D receptor and [delta]-aminolevulinic acid dehydratase genes.

Abstract

A cross-sectional study was performed to evaluate the influence of polymorphisms in the [delta]-aminolevulinic acid dehydratase (ALAD) and vitamin D receptor (VDR) genes on blood lead, tibia lead, and dimercaptosuccinic acid (DMSA)-chelatable lead levels in 798 lead workers and 135 controls without occupational lead exposure in the Republic of Korea. Tibia lead was assessed with a 30-min measurement by (109)Cd-induced K-shell X-ray fluorescence, and DMSA-chelatable lead was estimated as 4-hr urinary lead excretion after oral administration of 10 mg/kg DMSA. The primary goals of the analysis were to examine blood lead, tibia lead, and DMSA-chelatable lead levels by ALAD and VDR genotypes, controlling for covariates; and to evaluate whether ALAD and VDR genotype modified relations among the different lead biomarkers. There was a wide range of blood lead (4-86 microg/dL), tibia lead (-7-338 microg Pb/g bone mineral), and DMSA-chelatable lead (4.8-2,103 microg) levels among lead workers. Among lead workers, 9.9% (n = 79) were heterozygous for the ALAD(2) allele and there were no homozygotes. For VDR, 10.7% (n = 85) had the Bb genotype, and 0.5% (n = 4) had the BB genotype. Although the ALAD and VDR genes are located on different chromosomes, lead workers homozygous for the ALAD(1) allele were much less likely to have the VDR bb genotype (crude odds ratio = 0.29, 95% exact confidence interval = 0.06-0.91). In adjusted analyses, subjects with the ALAD(2) allele had higher blood lead levels (on average, 2.9 microg/dL, p = 0.07) but no difference in tibia lead levels compared with subjects without the allele. In adjusted analyses, lead workers with the VDR B allele had significantly (p < 0.05) higher blood lead levels (on average, 4.2 microg/dL), chelatable lead levels (on average, 37.3 microg), and tibia lead levels (on average, 6.4 microg/g) than did workers with the VDR bb genotype. The current data confirm past observations that the ALAD gene modifies the toxicokinetics of lead and also provides new evidence that the VDR gene does so as well.

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  • Authors+Show Affiliations

    ,

    Department of Environmental Health Sciences, Johns Hopkins School of Hygiene and Public Health, Baltimore, MD 21205, USA. bschwart@jhsph.edu

    , , , , ,

    Source

    Environmental health perspectives 108:10 2000 Oct pg 949-54

    MeSH

    Adolescent
    Adult
    Chelating Agents
    Cross-Sectional Studies
    Female
    Humans
    Lead
    Male
    Middle Aged
    Occupational Exposure
    Polymorphism, Genetic
    Porphobilinogen Synthase
    Receptors, Calcitriol
    Succimer
    Tibia
    Tissue Distribution

    Pub Type(s)

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

    Language

    eng

    PubMed ID

    11049814

    Citation

    Schwartz, B S., et al. "Associations of Blood Lead, Dimercaptosuccinic Acid-chelatable Lead, and Tibia Lead With Polymorphisms in the Vitamin D Receptor and [delta]-aminolevulinic Acid Dehydratase Genes." Environmental Health Perspectives, vol. 108, no. 10, 2000, pp. 949-54.
    Schwartz BS, Lee BK, Lee GS, et al. Associations of blood lead, dimercaptosuccinic acid-chelatable lead, and tibia lead with polymorphisms in the vitamin D receptor and [delta]-aminolevulinic acid dehydratase genes. Environ Health Perspect. 2000;108(10):949-54.
    Schwartz, B. S., Lee, B. K., Lee, G. S., Stewart, W. F., Simon, D., Kelsey, K., & Todd, A. C. (2000). Associations of blood lead, dimercaptosuccinic acid-chelatable lead, and tibia lead with polymorphisms in the vitamin D receptor and [delta]-aminolevulinic acid dehydratase genes. Environmental Health Perspectives, 108(10), pp. 949-54.
    Schwartz BS, et al. Associations of Blood Lead, Dimercaptosuccinic Acid-chelatable Lead, and Tibia Lead With Polymorphisms in the Vitamin D Receptor and [delta]-aminolevulinic Acid Dehydratase Genes. Environ Health Perspect. 2000;108(10):949-54. PubMed PMID: 11049814.
    * Article titles in AMA citation format should be in sentence-case
    TY - JOUR T1 - Associations of blood lead, dimercaptosuccinic acid-chelatable lead, and tibia lead with polymorphisms in the vitamin D receptor and [delta]-aminolevulinic acid dehydratase genes. AU - Schwartz,B S, AU - Lee,B K, AU - Lee,G S, AU - Stewart,W F, AU - Simon,D, AU - Kelsey,K, AU - Todd,A C, PY - 2000/10/26/pubmed PY - 2001/2/28/medline PY - 2000/10/26/entrez SP - 949 EP - 54 JF - Environmental health perspectives JO - Environ. Health Perspect. VL - 108 IS - 10 N2 - A cross-sectional study was performed to evaluate the influence of polymorphisms in the [delta]-aminolevulinic acid dehydratase (ALAD) and vitamin D receptor (VDR) genes on blood lead, tibia lead, and dimercaptosuccinic acid (DMSA)-chelatable lead levels in 798 lead workers and 135 controls without occupational lead exposure in the Republic of Korea. Tibia lead was assessed with a 30-min measurement by (109)Cd-induced K-shell X-ray fluorescence, and DMSA-chelatable lead was estimated as 4-hr urinary lead excretion after oral administration of 10 mg/kg DMSA. The primary goals of the analysis were to examine blood lead, tibia lead, and DMSA-chelatable lead levels by ALAD and VDR genotypes, controlling for covariates; and to evaluate whether ALAD and VDR genotype modified relations among the different lead biomarkers. There was a wide range of blood lead (4-86 microg/dL), tibia lead (-7-338 microg Pb/g bone mineral), and DMSA-chelatable lead (4.8-2,103 microg) levels among lead workers. Among lead workers, 9.9% (n = 79) were heterozygous for the ALAD(2) allele and there were no homozygotes. For VDR, 10.7% (n = 85) had the Bb genotype, and 0.5% (n = 4) had the BB genotype. Although the ALAD and VDR genes are located on different chromosomes, lead workers homozygous for the ALAD(1) allele were much less likely to have the VDR bb genotype (crude odds ratio = 0.29, 95% exact confidence interval = 0.06-0.91). In adjusted analyses, subjects with the ALAD(2) allele had higher blood lead levels (on average, 2.9 microg/dL, p = 0.07) but no difference in tibia lead levels compared with subjects without the allele. In adjusted analyses, lead workers with the VDR B allele had significantly (p < 0.05) higher blood lead levels (on average, 4.2 microg/dL), chelatable lead levels (on average, 37.3 microg), and tibia lead levels (on average, 6.4 microg/g) than did workers with the VDR bb genotype. The current data confirm past observations that the ALAD gene modifies the toxicokinetics of lead and also provides new evidence that the VDR gene does so as well. SN - 0091-6765 UR - https://www.unboundmedicine.com/medline/citation/11049814/Associations_of_blood_lead_dimercaptosuccinic_acid_chelatable_lead_and_tibia_lead_with_polymorphisms_in_the_vitamin_D_receptor_and_[delta]_aminolevulinic_acid_dehydratase_genes_ L2 - https://ehp.niehs.nih.gov/doi/full/10.1289/ehp.00108949?url_ver=Z39.88-2003&amp;rfr_id=ori:rid:crossref.org&amp;rfr_dat=cr_pub=pubmed DB - PRIME DP - Unbound Medicine ER -