Skip to main content
PMC home page
Environmental Health Perspectives logoLink to Environmental Health Perspectives
. 2004 Apr;112(5):538–541. doi: 10.1289/ehp.6464

The protective effect of delta-aminolevulinic acid dehydratase 1-2 and 2-2 isozymes against blood lead with higher hematologic parameters.

Hee-Seon Kim 1, Sung-Soo Lee 1, Gap-Soo Lee 1, Young Hwangbo 1, Kyu-Dong Ahn 1, Byung-Kook Lee 1
PMCID: PMC1241917  PMID: 15064157

Abstract

Previous studies have suggested that delta-aminolevulinic acid dehydratase (ALAD) types 1-2 or 2-2 are protective against the toxicity of blood lead (PbB) when zinc protoporphyrin (ZPP) levels are low because of differential binding of lead in erythrocytes. The hypothesis is that subjects with the ALAD 1-1 genotype are more susceptible to lead exposure with impaired hematologic synthesis and therefore that iron nutrition is more important in those with the ALAD 1-1 genotype. The purpose of this study was to prove the protective effect of ALAD 1-2/2-2 against PbB with higher hematologic parameters. Data on 1,219 male workers from eight lead-using factories in the Republic of Korea were examined in this cross-sectional study. Blood samples were evaluated for PbB, ZPP, hemoglobin (Hb), and serum iron (SFe) concentrations and ALAD genotypes. The overall prevalence of the ALAD 1-2/2-2 genotype was 9.3%, which was associated with lower log ZPP (p < 0.001) and higher Hb (p = 0.014) levels. For the subjects with normal iron status (SFe levels > 60 micro g/dL), those with the ALAD 1-1 genotype were more likely to be anemic (adjusted odds ratio of 5.2; 95% confidence interval, 1.2-22.6) than those with ALAD 1-2/2-2. The study confirms the protective effects of ALAD 1-2/2-2 polymorphisms against PbB on hematologic pathways. In order to promote health and to minimize the toxicity of lead exposure more effectively, the nutritional management of iron in Korean workers should take both their ALAD genotypes and occupational lead exposures into account.

Full Text

The Full Text of this article is available as a PDF (131.2 KB).

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Albahary C. Lead and hemopoiesis. The mechanism and consequences of the erythropathy of occupational lead poisoning. Am J Med. 1972 Mar;52(3):367–378. doi: 10.1016/0002-9343(72)90025-3. [DOI] [PubMed] [Google Scholar]
  2. Bergdahl I. A., Gerhardsson L., Schütz A., Desnick R. J., Wetmur J. G., Skerfving S. Delta-aminolevulinic acid dehydratase polymorphism: influence on lead levels and kidney function in humans. Arch Environ Health. 1997 Mar-Apr;52(2):91–96. doi: 10.1080/00039899709602870. [DOI] [PubMed] [Google Scholar]
  3. Blumberg W. E., Eisinger J., Lamola A. A., Zuckerman D. M. Zinc protoporphyrin level in blood determined by a portable hematofluorometer: a screening device for lead poisoning. J Lab Clin Med. 1977 Apr;89(4):712–723. [PubMed] [Google Scholar]
  4. Cheng Y., Willett W. C., Schwartz J., Sparrow D., Weiss S., Hu H. Relation of nutrition to bone lead and blood lead levels in middle-aged to elderly men. The Normative Aging Study. Am J Epidemiol. 1998 Jun 15;147(12):1162–1174. doi: 10.1093/oxfordjournals.aje.a009415. [DOI] [PubMed] [Google Scholar]
  5. Fleming D. E., Chettle D. R., Wetmur J. G., Desnick R. J., Robin J. P., Boulay D., Richard N. S., Gordon C. L., Webber C. E. Effect of the delta-aminolevulinate dehydratase polymorphism on the accumulation of lead in bone and blood in lead smelter workers. Environ Res. 1998 Apr;77(1):49–61. doi: 10.1006/enrs.1997.3818. [DOI] [PubMed] [Google Scholar]
  6. Goering P. L., Fowler B. A. Regulatory roles of high-affinity metal-binding proteins in mediating lead effects on delta-aminolevulinic acid dehydratase. Ann N Y Acad Sci. 1987;514:235–247. doi: 10.1111/j.1749-6632.1987.tb48778.x. [DOI] [PubMed] [Google Scholar]
  7. Hu H., Wu M. T., Cheng Y., Sparrow D., Weiss S., Kelsey K. 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 Aug;109(8):827–832. doi: 10.1289/ehp.01109827. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Kelada S. N., Shelton E., Kaufmann R. B., Khoury M. J. Delta-aminolevulinic acid dehydratase genotype and lead toxicity: a HuGE review. Am J Epidemiol. 2001 Jul 1;154(1):1–13. doi: 10.1093/aje/154.1.1. [DOI] [PubMed] [Google Scholar]
  9. Kim Hee Seon, Lee Sung Soo, Hwangbo Young, Ahn Kyu Dong, Lee Byung Kook. Cross-sectional study of blood lead effects on iron status in Korean lead workers. Nutrition. 2003 Jul-Aug;19(7-8):571–576. doi: 10.1016/s0899-9007(03)00035-2. [DOI] [PubMed] [Google Scholar]
  10. Lee B. K., Lee G. S., Stewart W. F., Ahn K. D., Simon D., Kelsey K. T., Todd A. C., Schwartz B. S. Associations of blood pressure and hypertension with lead dose measures and polymorphisms in the vitamin D receptor and delta-aminolevulinic acid dehydratase genes. Environ Health Perspect. 2001 Apr;109(4):383–389. doi: 10.1289/ehp.01109383. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Mahaffey K. R. Environmental lead toxicity: nutrition as a component of intervention. Environ Health Perspect. 1990 Nov;89:75–78. doi: 10.1289/ehp.908975. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Onalaja A. O., Claudio L. Genetic susceptibility to lead poisoning. Environ Health Perspect. 2000 Mar;108 (Suppl 1):23–28. doi: 10.1289/ehp.00108s123. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Schwartz B. S., Lee B. K., Lee G. S., Stewart W. F., Simon D., Kelsey K., Todd A. C. 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 Oct;108(10):949–954. doi: 10.1289/ehp.00108949. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Schwartz B. S., Lee B. K., Stewart W., Ahn K. D., Springer K., Kelsey K. Associations of delta-aminolevulinic acid dehydratase genotype with plant, exposure duration, and blood lead and zinc protoporphyrin levels in Korean lead workers. Am J Epidemiol. 1995 Oct 1;142(7):738–745. doi: 10.1093/oxfordjournals.aje.a117705. [DOI] [PubMed] [Google Scholar]
  15. Sithisarankul P., Schwartz B. S., Lee B. K., Kelsey K. T., Strickland P. T. Aminolevulinic acid dehydratase genotype mediates plasma levels of the neurotoxin, 5-aminolevulinic acid, in lead-exposed workers. Am J Ind Med. 1997 Jul;32(1):15–20. doi: 10.1002/(sici)1097-0274(199707)32:1<15::aid-ajim2>3.0.co;2-q. [DOI] [PubMed] [Google Scholar]
  16. Smith C. M., Wang X., Hu H., Kelsey K. T. A polymorphism in the delta-aminolevulinic acid dehydratase gene may modify the pharmacokinetics and toxicity of lead. Environ Health Perspect. 1995 Mar;103(3):248–253. doi: 10.1289/ehp.95103248. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Wetmur J. G. Influence of the common human delta-aminolevulinate dehydratase polymorphism on lead body burden. Environ Health Perspect. 1994 Sep;102 (Suppl 3):215–219. doi: 10.1289/ehp.94102s3215. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Wetmur J. G., Kaya A. H., Plewinska M., Desnick R. J. Molecular characterization of the human delta-aminolevulinate dehydratase 2 (ALAD2) allele: implications for molecular screening of individuals for genetic susceptibility to lead poisoning. Am J Hum Genet. 1991 Oct;49(4):757–763. [PMC free article] [PubMed] [Google Scholar]
  19. Wetmur J. G., Lehnert G., Desnick R. J. The delta-aminolevulinate dehydratase polymorphism: higher blood lead levels in lead workers and environmentally exposed children with the 1-2 and 2-2 isozymes. Environ Res. 1991 Dec;56(2):109–119. doi: 10.1016/s0013-9351(05)80001-5. [DOI] [PubMed] [Google Scholar]
  20. Ziemsen B., Angerer J., Lehnert G., Benkmann H. G., Goedde H. W. Polymorphism of delta-aminolevulinic acid dehydratase in lead-exposed workers. Int Arch Occup Environ Health. 1986;58(3):245–247. doi: 10.1007/BF00432107. [DOI] [PubMed] [Google Scholar]

Articles from Environmental Health Perspectives are provided here courtesy of National Institute of Environmental Health Sciences

RESOURCES