Skip to main content

Advertisement

Log in

A polymorphism in the delta-aminolevulinic acid dehydratase gene modifies plasma/whole blood lead ratio

  • Inorganic Compounds
  • Published:
Archives of Toxicology Aims and scope Submit manuscript

Abstract

Delta aminolevulinic acid dehydratase (ALAD) plays an important role in lead poisoning. This study was carried out to examine the effects of ALAD gene polymorphism (G177C) on %Pb-P(plasma lead)/Pb-B(whole blood) ratio in 142 subjects environmentally exposed to lead. Genotypes for the ALAD G177C polymorphism were determined by PCR and restriction fragment length digestion. Pb-P and Pb-B were determined by inductively coupled plasma mass spectrometry and by graphite furnace atomic absorption spectrometry, respectively. The allele frequencies for ALAD1 and ALAD2 alleles were 0.897 and 0.103, respectively. We combined both ALAD 1-2 and ALAD 2-2 genotypes together (ALAD 1-2/2-2 group) and compared with the ALAD 1-1 genotype group. While no significant differences were found in Pb-B, subjects from the ALAD 1-2/2-2 genotype group presented significantly higher Pb-P concentrations and %Pb-P/Pb-B ratios (0.89±0.07 μg/l, and 1.45±0.10%, respectively) when compared with subjects from the ALAD 1-1 genotype group (0.44±0.05 μg/l, and 0.48±0.02, respectively; both P<0.0001). The higher %Pb-P/Pb-B ratios in carriers of the ALAD-2 allele compared with noncarriers indicate that ALAD 1-2/2-2 subjects are probably at increased health risks associated with lead exposure.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1

Similar content being viewed by others

References

  • Astrin KH, Bishop DF, Wetmur JG, Kaul B, Davidow B, Desnick RJ (1987) delta-Aminolevulinic acid dehydratase isozymes and lead toxicity. Ann NY Acad Sci 514:23–29

    Article  PubMed  CAS  Google Scholar 

  • Barbosa F Jr, Tanus-Santos JE, Gerlach RF, Parsons PJ (2005) Current needs and limitations on the use of biomarkers of internal dose to diagnose lead exposure. Environ Health Perspect 113:1669–1674

    Google Scholar 

  • Barbosa F Jr, Sandrim VC, Uzuelli JA, Gerlach RF, Tanus-Santos JE (2006) eNOS genotype-dependent correlation between whole blood lead and plasma nitric oxide products concentrations. Nitric Oxide (in press)

  • Battistuzzi G, Petrucci R, Silvagni L, Urbani FR, Caiola S (1981) delta-Aminolevulinate dehydrase: a new genetic polymorphism in man. Ann Hum Genet 45:223–229

    Article  PubMed  CAS  Google Scholar 

  • Bergdahl IA, Grubb A, Schutz A, Desnick RJ, Wetmur JG, Sassa S, Skerfving S (1997) Lead binding to delta-aminolevulinic acid dehydratase (ALAD) in human erythrocytes. Pharmacol Toxicol 81:153–158

    Article  PubMed  CAS  Google Scholar 

  • Bergdahl IA, Vahter M, Counter SA, Schutz A, Buchanan LH, Ortega F, Laurell G, Skerfving S (1999) Lead in plasma and whole blood from lead-exposed children. Environ Res 80:25–33

    Article  PubMed  CAS  Google Scholar 

  • Cake KM, Bowins RJ, Vaillancourt C, Gordon CL, McNutt RH, Laporte R, Webber CE, Chettle DR (1996) Partition of circulating lead between serum and red cells is different for internal and external sources of lead. Am J Ind Med 29:440–445

    Article  PubMed  CAS  Google Scholar 

  • Fleming DE, Chettle DR, Wetmur JG, Desnick RJ, Robin JP, Boulay D, Richard NS, Gordon CL, Webber CE (1998) Effect of the delta-aminolevulinate dehydratase polymorphism on the accumulation of lead in bone and blood in lead smelter workers. Environ Res 77:49–61

    Article  PubMed  CAS  Google Scholar 

  • Hernandez-Avila M, Smith D, Meneses F, Sanin LH, Hu H (1998) The influence of bone and blood lead on plasma lead levels in environmentally exposed adults. Environ Health Perspect 106:473–477

    Article  PubMed  CAS  Google Scholar 

  • Hu H, Wu MT, 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. Environ Health Perspect 109:827–832

    Article  PubMed  CAS  Google Scholar 

  • Kelada SN, Shelton E, Kaufmann RB, Khoury MJ (2001) Delta-aminolevulinic acid dehydratase genotype and lead toxicity: a HuGE review. Am J Epidemiol 154:1–13

    Article  PubMed  CAS  Google Scholar 

  • Perez-Bravo F, Ruz M, Moran-Jimenez MJ, Olivares M, Rebolledo A, Codoceo J, Sepulveda V, Jenkin A, Santos JL, Fontanellas A (2004) Association between aminolevulinate dehydrase genotypes and blood lead levels in children from a lead-contaminated area in Antofagasta, Chile. Arch Environ Contam Toxicol 47:276–280

    Article  PubMed  CAS  Google Scholar 

  • Schutz A, Bergdahl IA, Ekholm A, Skerfving S (1996) Measurement by ICP-MS of lead in plasma and whole blood of lead workers and controls. Occup Environ Med 53:736–740

    Article  PubMed  CAS  Google Scholar 

  • Schwartz BS, Lee BK, Stewart W, Ahn KD, Springer K, Kelsey K (1995) 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 142:738–745

    PubMed  CAS  Google Scholar 

  • Shen XM, Wu SH, Yan CH, Zhao W, Ao LM, Zhang YW, He JM, Ying JM, Li RQ, Wu SM, Guo D (2001) Delta-aminolevulinate dehydratase polymorphism and blood lead levels in Chinese children. Environ Res 85:185–190

    Article  PubMed  CAS  Google Scholar 

  • Smith CM, Wang X, Hu H, Kelsey KT (1995) A polymorphism in the delta-aminolevulinic acid dehydratase gene may modify the pharmacokinetics and toxicity of lead. Environ Health Perspect 103:248–253

    Article  PubMed  CAS  Google Scholar 

  • Smith D, Hernandez-Avila M, Tellez-Rojo MM, Mercado A, Hu H (2002) The relationship between lead in plasma and whole blood in women. Environ Health Perspect 110:263–268

    Article  PubMed  CAS  Google Scholar 

  • Suzen HS, Duydu Y, Aydin A, Isimer A, Vural N (2003) Influence of the delta-aminolevulinic acid dehydratase (ALAD) polymorphism on biomarkers of lead exposure in Turkish storage battery manufacturing workers. Am J Ind Med 43:165–171

    Article  PubMed  CAS  Google Scholar 

  • Wetmur JG, Kaya AH, Plewinska M, Desnick RJ (1991a) 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 49:757–763

    CAS  Google Scholar 

  • Wetmur JG, Lehnert G, Desnick RJ (1991b) 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 56:109–119

    Article  CAS  Google Scholar 

  • Zhou Y, Zanao RA, Barbosa F, Parsons PJ, Krug FJ (2002) Investigations on a W-Rh permanent modifier for the detection of Pb in blood by electrothermal atomic absorption spectrometry. Spectrochim Acta Part B 57:1291–1300

    Article  Google Scholar 

  • Ziemsen B, Angerer J, Lehnert G, Benkmann HG, Goedde HW (1986) Polymorphism of delta-aminolevulinic acid dehydratase in lead-exposed workers. Int Arch Occup Environ Health 58:245–247

    Article  PubMed  CAS  Google Scholar 

Download references

Acknowledgments

This study was supported by Fundação de Amparo a Pesquisa do Estado de São Paulo (FAPESP), Coordenadoria de Aperfeiçoamento de Pessoal de Nível Superior (CAPES), and Conselho Nacional de Desenvolvimento e Cientifico e Tecnológico (CNPq).

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Jose E. Tanus-Santos.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Montenegro, M.F., Barbosa , F., Sandrim, V.C. et al. A polymorphism in the delta-aminolevulinic acid dehydratase gene modifies plasma/whole blood lead ratio. Arch Toxicol 80, 394–398 (2006). https://doi.org/10.1007/s00204-005-0056-y

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00204-005-0056-y

Keywords

Navigation