Tags

Type your tag names separated by a space and hit enter

The delta-aminolevulinic acid dehydratase (ALAD) polymorphism and bone and blood lead levels in community-exposed men: the Normative Aging Study.

Abstract

Recent research has indicated that a polymorphic variant of delta-aminolevulinic acid dehydratase (ALAD) may influence an individual's level of lead in bone and blood and, as a result, may also influence an individual's susceptibility to lead toxicity. In this study, we investigated whether this ALAD polymorphism is associated with altered levels of lead in bone and blood among 726 middle-aged and elderly men who had community (nonoccupational) exposures to lead. We measured levels of blood and bone lead by graphite furnace atomic absorption spectroscopy and a K X-ray fluorescence (KXRF) instrument, respectively. We determined the ALAD MspI polymorphism in exon 4 by a polymerase chain reaction restriction fragment length polymorphism (RFLP). Of the 726 subjects, 7 (1%) and 111 (15%) were, respectively, homozygous and heterozygous for the variant allele. The mean (SD) of blood lead (micrograms per deciliter), cortical bone (tibia) lead (micrograms per gram), and trabecular bone (patella) lead (micrograms per gram) were 6.2 (4.1), 22.1 (13.5), and 31.9 (19.5) in subjects who did not have the variant allele (ALAD 1-1), and 5.7 (4.2), 21.2 (10.9), and 30.4 (17.2) in the combined subjects who were either heterozygous or homozygous for the variant allele (ALAD 1-2 and ALAD 2-2). In multivariate linear regression models that controlled for age, education, smoking, alcohol ingestion, and vitamin D intake, the ALAD 1-1 genotype was associated with cortical bone lead levels that were 2.55 microg/g [95% confidence interval (CI) 0.05-5.05] higher than those of the variant allele carriers. We found no significant differences by genotype with respect to lead levels in trabecular bone or blood. In stratified analyses and a multivariate regression model that tested for interaction, the relationship of trabecular bone lead to blood lead appeared to be significantly modified by ALAD genotype, with variant allele carriers having higher blood lead levels, but only when trabecular bone lead levels exceeded 60 microg/g. These results suggest that the variant ALAD-2 allele modifies lead kinetics possibly by decreasing lead uptake into cortical bone and increasing the mobilization of lead from trabecular bone.

Links

  • PMC Free PDF
  • PMC Free Full Text
  • FREE Publisher Full Text
  • Authors+Show Affiliations

    ,

    Occupational Health Program, Department of Environmental Health, Harvard School of Public Health, Boston, Massachusetts 02115, USA. howard.hu@channing.harvard.edu

    , , , ,

    Source

    Environmental health perspectives 109:8 2001 Aug pg 827-32

    MeSH

    Aged
    Aging
    Bone and Bones
    Environmental Exposure
    Genetic Predisposition to Disease
    Genotype
    Humans
    Lead
    Lead Poisoning
    Longitudinal Studies
    Male
    Massachusetts
    Middle Aged
    Patella
    Polymorphism, Genetic
    Porphobilinogen Synthase
    Smoking
    Socioeconomic Factors
    Tibia
    Vitamin D

    Pub Type(s)

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

    Language

    eng

    PubMed ID

    11564619

    Citation

    Hu, H, et al. "The Delta-aminolevulinic Acid Dehydratase (ALAD) Polymorphism and Bone and Blood Lead Levels in Community-exposed Men: the Normative Aging Study." Environmental Health Perspectives, vol. 109, no. 8, 2001, pp. 827-32.
    Hu H, Wu MT, Cheng Y, et al. The delta-aminolevulinic acid dehydratase (ALAD) polymorphism and bone and blood lead levels in community-exposed men: the Normative Aging Study. Environ Health Perspect. 2001;109(8):827-32.
    Hu, H., Wu, M. T., Cheng, Y., Sparrow, D., Weiss, S., & Kelsey, K. (2001). The delta-aminolevulinic acid dehydratase (ALAD) polymorphism and bone and blood lead levels in community-exposed men: the Normative Aging Study. Environmental Health Perspectives, 109(8), pp. 827-32.
    Hu H, et al. The Delta-aminolevulinic Acid Dehydratase (ALAD) Polymorphism and Bone and Blood Lead Levels in Community-exposed Men: the Normative Aging Study. Environ Health Perspect. 2001;109(8):827-32. PubMed PMID: 11564619.
    * Article titles in AMA citation format should be in sentence-case
    TY - JOUR T1 - The delta-aminolevulinic acid dehydratase (ALAD) polymorphism and bone and blood lead levels in community-exposed men: the Normative Aging Study. AU - Hu,H, AU - Wu,M T, AU - Cheng,Y, AU - Sparrow,D, AU - Weiss,S, AU - Kelsey,K, PY - 2001/9/21/pubmed PY - 2002/1/26/medline PY - 2001/9/21/entrez SP - 827 EP - 32 JF - Environmental health perspectives JO - Environ. Health Perspect. VL - 109 IS - 8 N2 - Recent research has indicated that a polymorphic variant of delta-aminolevulinic acid dehydratase (ALAD) may influence an individual's level of lead in bone and blood and, as a result, may also influence an individual's susceptibility to lead toxicity. In this study, we investigated whether this ALAD polymorphism is associated with altered levels of lead in bone and blood among 726 middle-aged and elderly men who had community (nonoccupational) exposures to lead. We measured levels of blood and bone lead by graphite furnace atomic absorption spectroscopy and a K X-ray fluorescence (KXRF) instrument, respectively. We determined the ALAD MspI polymorphism in exon 4 by a polymerase chain reaction restriction fragment length polymorphism (RFLP). Of the 726 subjects, 7 (1%) and 111 (15%) were, respectively, homozygous and heterozygous for the variant allele. The mean (SD) of blood lead (micrograms per deciliter), cortical bone (tibia) lead (micrograms per gram), and trabecular bone (patella) lead (micrograms per gram) were 6.2 (4.1), 22.1 (13.5), and 31.9 (19.5) in subjects who did not have the variant allele (ALAD 1-1), and 5.7 (4.2), 21.2 (10.9), and 30.4 (17.2) in the combined subjects who were either heterozygous or homozygous for the variant allele (ALAD 1-2 and ALAD 2-2). In multivariate linear regression models that controlled for age, education, smoking, alcohol ingestion, and vitamin D intake, the ALAD 1-1 genotype was associated with cortical bone lead levels that were 2.55 microg/g [95% confidence interval (CI) 0.05-5.05] higher than those of the variant allele carriers. We found no significant differences by genotype with respect to lead levels in trabecular bone or blood. In stratified analyses and a multivariate regression model that tested for interaction, the relationship of trabecular bone lead to blood lead appeared to be significantly modified by ALAD genotype, with variant allele carriers having higher blood lead levels, but only when trabecular bone lead levels exceeded 60 microg/g. These results suggest that the variant ALAD-2 allele modifies lead kinetics possibly by decreasing lead uptake into cortical bone and increasing the mobilization of lead from trabecular bone. SN - 0091-6765 UR - https://www.unboundmedicine.com/medline/citation/11564619/The_delta_aminolevulinic_acid_dehydratase__ALAD__polymorphism_and_bone_and_blood_lead_levels_in_community_exposed_men:_the_Normative_Aging_Study_ L2 - https://ehp.niehs.nih.gov/doi/full/10.1289/ehp.01109827?url_ver=Z39.88-2003&rfr_id=ori:rid:crossref.org&rfr_dat=cr_pub=pubmed DB - PRIME DP - Unbound Medicine ER -