Interaction of blood lead and δ-aminolevulinic acid dehydratase genotype on markers of heme synthesis and sperm production in lead smelter workers

Bruce H. Alexander, Harvey Checkoway, Paola Costa-Mallen, Elaine M. Faustman, James S. Woods, Karl T. Kelsey, Chris Van Netten, Lucio G. Costa

Research output: Contribution to journalArticlepeer-review

64 Scopus citations

Abstract

The gene that encodes δ-aminolevulinic acid dehydratase (ALAD) has a polymorphism that may modify lead toxicokinetics and ultimately influence individual susceptibility to lead poisoning. To evaluate the effect of the ALAD polymorphism on lead-mediated outcomes, a cross-sectional study of male employees from a lead-zinc smelter compared associations between blood lead concentration and markers of heme synthesis and semen quality with respect to ALAD genotype. Male employees were recruited via postal questionnaire to donate blood and urine for analysis of blood lead, zinc protoporphyrin (ZPP), urinary coproporphyrin (CPU), and ALAD genotype, and semen samples for semen analysis. Of the 134 workers who had ALAD genotypes completed, 114 (85%) were ALAD1-1 (ALAD1) and 20 (15%) were ALAD1-2 (ALAD2). The mean blood lead concentrations for ALAD1 and ALAD2 were 23.1 and 28.4 μg/dl (p = 0.08), respectively. ZPP/heme ratios were higher in ALAD1 workers (68.6 vs. 57.8 μmol/mol; p = 0.14), and the slope of the blood lead ZPP linear relationship was greater for ALAD1 (2.83 vs. 1.50, p = 0.06). No linear relationship between CPU and blood lead concentration was observed for either ALAD1 or ALAD2. The associations of blood lead concentration with ZPP, CPU, sperm count, and sperm concentration were more evident in workers with the ALAD1 genotype and blood lead concentrations > 40 μg/dl. The ALAD generic polymorphism appears to modify the association between blood lead concentration and ZPP. However, consistent modification of effects were not found for CPU, sperm count, or sperm concentration.

Original languageEnglish (US)
Pages (from-to)213-216
Number of pages4
JournalEnvironmental health perspectives
Volume106
Issue number4
DOIs
StatePublished - 1998

Keywords

  • Coproporphyrin
  • Genotype
  • Lead
  • Semen
  • Smelters
  • Zinc protoporphyrin
  • δ-aminolevulinic acid dehydratase

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