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. 2001 Aug;109(8):827–832. doi: 10.1289/ehp.01109827

The delta-aminolevulinic acid dehydratase (ALAD) polymorphism and bone and blood lead levels in community-exposed men: the Normative Aging Study.

H Hu 1, M T Wu 1, Y Cheng 1, D Sparrow 1, S Weiss 1, K Kelsey 1
PMCID: PMC1240411  PMID: 11564619

Abstract

Recent research has indicated that a polymorphic variant of delta-aminolevulinic acid dehydratase (ALAD) may influence an individual's level of lead in bone and blood and, as a result, may also influence an individual's susceptibility to lead toxicity. In this study, we investigated whether this ALAD polymorphism is associated with altered levels of lead in bone and blood among 726 middle-aged and elderly men who had community (nonoccupational) exposures to lead. We measured levels of blood and bone lead by graphite furnace atomic absorption spectroscopy and a K X-ray fluorescence (KXRF) instrument, respectively. We determined the ALAD MspI polymorphism in exon 4 by a polymerase chain reaction restriction fragment length polymorphism (RFLP). Of the 726 subjects, 7 (1%) and 111 (15%) were, respectively, homozygous and heterozygous for the variant allele. The mean (SD) of blood lead (micrograms per deciliter), cortical bone (tibia) lead (micrograms per gram), and trabecular bone (patella) lead (micrograms per gram) were 6.2 (4.1), 22.1 (13.5), and 31.9 (19.5) in subjects who did not have the variant allele (ALAD 1-1), and 5.7 (4.2), 21.2 (10.9), and 30.4 (17.2) in the combined subjects who were either heterozygous or homozygous for the variant allele (ALAD 1-2 and ALAD 2-2). In multivariate linear regression models that controlled for age, education, smoking, alcohol ingestion, and vitamin D intake, the ALAD 1-1 genotype was associated with cortical bone lead levels that were 2.55 microg/g [95% confidence interval (CI) 0.05-5.05] higher than those of the variant allele carriers. We found no significant differences by genotype with respect to lead levels in trabecular bone or blood. In stratified analyses and a multivariate regression model that tested for interaction, the relationship of trabecular bone lead to blood lead appeared to be significantly modified by ALAD genotype, with variant allele carriers having higher blood lead levels, but only when trabecular bone lead levels exceeded 60 microg/g. These results suggest that the variant ALAD-2 allele modifies lead kinetics possibly by decreasing lead uptake into cortical bone and increasing the mobilization of lead from trabecular bone.

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Selected References

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  1. Alexander B. H., Checkoway H., Costa-Mallen P., Faustman E. M., Woods J. S., Kelsey K. T., van Netten C., Costa L. G. Interaction of blood lead and delta-aminolevulinic acid dehydratase genotype on markers of heme synthesis and sperm production in lead smelter workers. Environ Health Perspect. 1998 Apr;106(4):213–216. doi: 10.1289/ehp.98106213. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Battistuzzi G., Petrucci R., Silvagni L., Urbani F. R., Caiola S. delta-Aminolevulinate dehydrase: a new genetic polymorphism in man. Ann Hum Genet. 1981 Jul;45(Pt 3):223–229. doi: 10.1111/j.1469-1809.1981.tb00333.x. [DOI] [PubMed] [Google Scholar]
  3. Bellinger D., Hu H., Titlebaum L., Needleman H. L. Attentional correlates of dentin and bone lead levels in adolescents. Arch Environ Health. 1994 Mar-Apr;49(2):98–105. doi: 10.1080/00039896.1994.9937461. [DOI] [PubMed] [Google Scholar]
  4. 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]
  5. Bergdahl I. A., Grubb A., Schütz A., Desnick R. J., Wetmur J. G., Sassa S., Skerfving S. Lead binding to delta-aminolevulinic acid dehydratase (ALAD) in human erythrocytes. Pharmacol Toxicol. 1997 Oct;81(4):153–158. doi: 10.1111/j.1600-0773.1997.tb02061.x. [DOI] [PubMed] [Google Scholar]
  6. Burger D. E., Milder F. L., Morsillo P. R., Adams B. B., Hu H. Automated bone lead analysis by K-x-ray fluorescence for the clinical environment. Basic Life Sci. 1990;55:287–292. doi: 10.1007/978-1-4613-1473-8_39. [DOI] [PubMed] [Google Scholar]
  7. Cheng Y., Schwartz J., Vokonas P. S., Weiss S. T., Aro A., Hu H. Electrocardiographic conduction disturbances in association with low-level lead exposure (the Normative Aging Study). Am J Cardiol. 1998 Sep 1;82(5):594–599. doi: 10.1016/s0002-9149(98)00402-0. [DOI] [PubMed] [Google Scholar]
  8. 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]
  9. 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]
  10. Hu H., Aro A., Payton M., Korrick S., Sparrow D., Weiss S. T., Rotnitzky A. The relationship of bone and blood lead to hypertension. The Normative Aging Study. JAMA. 1996 Apr 17;275(15):1171–1176. [PubMed] [Google Scholar]
  11. Hu H. Bone lead as a new biologic marker of lead dose: recent findings and implications for public health. Environ Health Perspect. 1998 Aug;106 (Suppl 4):961–967. doi: 10.1289/ehp.98106s4961. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Hu H., Payton M., Korrick S., Aro A., Sparrow D., Weiss S. T., Rotnitzky A. Determinants of bone and blood lead levels among community-exposed middle-aged to elderly men. The normative aging study. Am J Epidemiol. 1996 Oct 15;144(8):749–759. doi: 10.1093/oxfordjournals.aje.a008999. [DOI] [PubMed] [Google Scholar]
  13. 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]
  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. 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]
  16. Wetmur J. G., Bishop D. F., Cantelmo C., Desnick R. J. Human delta-aminolevulinate dehydratase: nucleotide sequence of a full-length cDNA clone. Proc Natl Acad Sci U S A. 1986 Oct;83(20):7703–7707. doi: 10.1073/pnas.83.20.7703. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. 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]
  18. 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]
  19. 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]

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