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Delta-aminolevulinic acid dehydratase genotype and lead toxicity: a HuGE review.

Abstract

The ALAD gene (chromosome 9q34) codes for delta-aminolevulinic acid dehydratase (ALAD) (E.C. 4.2.1.24). ALAD catalyzes the second step of heme synthesis and is polymorphic. The ALAD G177C polymorphism yields two codominant alleles, ALAD-1 and ALAD-2, and it has been implicated in susceptibility to lead toxicity. Genotype frequencies vary by geography and race. The rarer ALAD-2 allele has been associated with high blood lead levels and has been thought to increase the risk of lead toxicity by generating a protein that binds lead more tightly than the ALAD-1 protein. Other evidence suggests that ALAD-2 may confer resistance to the harmful effects of lead by sequestering lead, making it unavailable for pathophysiologic participation. Recent studies have shown that individuals who are homozygous for the ALAD-1 allele have higher cortical bone lead levels; this implies that they may have a greater body lead burden and may be at higher risk of the long-term effects of lead. Individuals exposed to lead in occupational settings have been the most frequent subjects of study. Genotype selection bias may limit inferences from these studies. No firm evidence exists for an association between ALAD genotype and susceptibility to lead toxicity at background exposure levels; therefore, population testing for the ALAD polymorphism is not justified.

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  • Authors+Show Affiliations

    ,

    Office of Genetics and Disease Prevention, Centers for Disease Control and Prevention, Atlanta, GA, USA. skelada@u.washington.edu

    , ,

    Source

    American journal of epidemiology 154:1 2001 Jul 01 pg 1-13

    MeSH

    Gene Frequency
    Genetic Predisposition to Disease
    Genome, Human
    Genotype
    Humans
    Lead Poisoning
    Molecular Structure
    Polymorphism, Genetic
    Porphobilinogen Synthase

    Pub Type(s)

    Journal Article
    Review

    Language

    eng

    PubMed ID

    11427399

    Citation

    Kelada, S N., et al. "Delta-aminolevulinic Acid Dehydratase Genotype and Lead Toxicity: a HuGE Review." American Journal of Epidemiology, vol. 154, no. 1, 2001, pp. 1-13.
    Kelada SN, Shelton E, Kaufmann RB, et al. Delta-aminolevulinic acid dehydratase genotype and lead toxicity: a HuGE review. Am J Epidemiol. 2001;154(1):1-13.
    Kelada, S. N., Shelton, E., Kaufmann, R. B., & Khoury, M. J. (2001). Delta-aminolevulinic acid dehydratase genotype and lead toxicity: a HuGE review. American Journal of Epidemiology, 154(1), pp. 1-13.
    Kelada SN, et al. Delta-aminolevulinic Acid Dehydratase Genotype and Lead Toxicity: a HuGE Review. Am J Epidemiol. 2001 Jul 1;154(1):1-13. PubMed PMID: 11427399.
    * Article titles in AMA citation format should be in sentence-case
    TY - JOUR T1 - Delta-aminolevulinic acid dehydratase genotype and lead toxicity: a HuGE review. AU - Kelada,S N, AU - Shelton,E, AU - Kaufmann,R B, AU - Khoury,M J, PY - 2001/6/28/pubmed PY - 2001/7/28/medline PY - 2001/6/28/entrez SP - 1 EP - 13 JF - American journal of epidemiology JO - Am. J. Epidemiol. VL - 154 IS - 1 N2 - The ALAD gene (chromosome 9q34) codes for delta-aminolevulinic acid dehydratase (ALAD) (E.C. 4.2.1.24). ALAD catalyzes the second step of heme synthesis and is polymorphic. The ALAD G177C polymorphism yields two codominant alleles, ALAD-1 and ALAD-2, and it has been implicated in susceptibility to lead toxicity. Genotype frequencies vary by geography and race. The rarer ALAD-2 allele has been associated with high blood lead levels and has been thought to increase the risk of lead toxicity by generating a protein that binds lead more tightly than the ALAD-1 protein. Other evidence suggests that ALAD-2 may confer resistance to the harmful effects of lead by sequestering lead, making it unavailable for pathophysiologic participation. Recent studies have shown that individuals who are homozygous for the ALAD-1 allele have higher cortical bone lead levels; this implies that they may have a greater body lead burden and may be at higher risk of the long-term effects of lead. Individuals exposed to lead in occupational settings have been the most frequent subjects of study. Genotype selection bias may limit inferences from these studies. No firm evidence exists for an association between ALAD genotype and susceptibility to lead toxicity at background exposure levels; therefore, population testing for the ALAD polymorphism is not justified. SN - 0002-9262 UR - https://www.unboundmedicine.com/medline/citation/11427399/Delta_aminolevulinic_acid_dehydratase_genotype_and_lead_toxicity:_a_HuGE_review_ L2 - https://academic.oup.com/aje/article-lookup/doi/10.1093/aje/154.1.1 DB - PRIME DP - Unbound Medicine ER -