American Journal of Epidemiology Vol. 154, No. 1 : 1-13
Copyright © 2001 by The Johns Hopkins University School of Hygiene and Public Health
HUMAN GENOME EPIDEMIOLOGY (HuGE) REVIEWS |
-Aminolevulinic Acid Dehydratase Genotype and Lead Toxicity: A HuGE Review
1 Office of Genetics and Disease Prevention, Centers for Disease Control and Prevention, Atlanta, GA.
2 Department of Environmental Health Sciences, School of Public Health, University of Michigan, Ann Arbor, MI.
3 Lead Poisoning Prevention Branch, Division of Environmental Hazards and Health Effects, National Center for Environmental Health, Centers for Disease Control and Prevention, Atlanta, GA.
4 Current address: Department of Environmental Health, School of Public Health and Community Medicine, University of Washington, Seattle, WA.
ABSTRACT
The ALAD gene (chromosome 9q34) codes for 
-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.
ALAD; aminolevulinic acid; epidemiology; genetic predisposition to disease; genetics; lead; lead poisoning; porphobilinogen synthase
Abbreviations: ALAD, aminolevulinic acid dehydratase; DMSA, dimercaptosuccinic acid; HFE, hereditary hemochromatosis gene; NHANES, National Health and Nutrition Examination Survey; SD, standard deviation; VDR, vitamin D receptor
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