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Archives of Toxicology

, Volume 80, Issue 7, pp 394–398 | Cite as

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

  • Marcelo F. Montenegro
  • Fernando Barbosa Jr
  • Valeria C. Sandrim
  • Raquel F. Gerlach
  • Jose E. Tanus-SantosEmail author
Inorganic Compounds

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.

Keywords

ALAD polymorphism Delta aminolevulinic acid dehydratase Lead toxicology Plasma lead Whole blood lead Plasma/whole blood lead ratio 

Notes

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).

References

  1. 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 514:23–29PubMedCrossRefGoogle Scholar
  2. 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 113:1669–1674Google Scholar
  3. 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)Google Scholar
  4. Battistuzzi G, Petrucci R, Silvagni L, Urbani FR, Caiola S (1981) delta-Aminolevulinate dehydrase: a new genetic polymorphism in man. Ann Hum Genet 45:223–229PubMedCrossRefGoogle Scholar
  5. 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 81:153–158PubMedCrossRefGoogle Scholar
  6. 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 80:25–33CrossRefPubMedGoogle Scholar
  7. 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 29:440–445CrossRefPubMedGoogle Scholar
  8. 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 77:49–61CrossRefPubMedGoogle Scholar
  9. 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 106:473–477PubMedCrossRefGoogle Scholar
  10. 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 109:827–832PubMedCrossRefGoogle Scholar
  11. Kelada SN, Shelton E, Kaufmann RB, Khoury MJ (2001) Delta-aminolevulinic acid dehydratase genotype and lead toxicity: a HuGE review. Am J Epidemiol 154:1–13CrossRefPubMedGoogle Scholar
  12. 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 47:276–280PubMedCrossRefGoogle Scholar
  13. 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 53:736–740PubMedCrossRefGoogle Scholar
  14. 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 142:738–745PubMedGoogle Scholar
  15. 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 85:185–190CrossRefPubMedGoogle Scholar
  16. 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 103:248–253PubMedCrossRefGoogle Scholar
  17. 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 110:263–268PubMedCrossRefGoogle Scholar
  18. 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 43:165–171CrossRefPubMedGoogle Scholar
  19. 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 49:757–763Google Scholar
  20. 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 56:109–119CrossRefGoogle Scholar
  21. 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 57:1291–1300CrossRefGoogle Scholar
  22. 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 58:245–247CrossRefPubMedGoogle Scholar

Copyright information

© Springer-Verlag 2005

Authors and Affiliations

  • Marcelo F. Montenegro
    • 1
  • Fernando Barbosa Jr
    • 1
    • 2
  • Valeria C. Sandrim
    • 1
  • Raquel F. Gerlach
    • 3
  • Jose E. Tanus-Santos
    • 1
    Email author
  1. 1.Department of Pharmacology, Faculty of Medicine of Ribeirao PretoUniversity of Sao PauloRibeirao Preto, SPBrazil
  2. 2.Department of Clinical, Toxicological and Food Science AnalysisFaculty of Pharmaceutical Sciences of Ribeirao PretoRibeirao Preto, SPBrazil
  3. 3.Department of Morphology, Estomatology and PhysiologyDental School of Ribeirao Preto, University of Sao PauloRibeirao Preto, SPBrazil

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