Aminolevulinic acid dehydratase genotype mediates plasma levels of the neurotoxin, 5-aminolevulinic acid, in lead-exposed workers

Pornchai Sithisarankul, Brian S. Schwartz, Byung Kook Lee, Karl T. Kelsey, Paul T. Strickland

Research output: Contribution to journalArticlepeer-review

Abstract

The first intermediate substrate in the heme synthetic pathway, 5- aminolevulinic acid (ALA), is neurotoxic in animal models and may be responsible for some of the adverse neurologic outcomes in lead poisoning and porphyria in adult humans. ALA is a substrate for the enzyme aminolevulinic acid dehydratase (ALAD; EC 4.2.1.24), which is encoded by the ALAD gene containing 2 co-dominant alleles, 1 and 2. We measured plasma ALA (ALAP) and urinary ALA (ALAU) in 65 Korean lead workers, of whom 44 were homozygous for ALAD1 (ALAD1-1 genotype) and 21 were heterozygous for ALAD (ALAD1-2 genotype). ALAP in subjects with the ALAD1-1 genotype was significantly higher than in those with the ALAD1-2 genotype (Wilcoxon rank sum test, P = 0.01). No difference between ALAD genotypes was found for age, zinc protoporphyrin (ZPP), blood lead levels (PbB), ALAU, or ALAU adjusted for creatinine. ALAP was significantly correlated with ZPP (Spearman's r = 0.38, P = 0.002) and with PbB (r = 0.34, P = 0.006), and marginally with employment duration (r = 0.22, P = 0.08). ALAP remained significantly elevated (P = 0.032) in ALAD1-1 subjects after adjustment for PbB and age by multiple linear regression. These results suggest that ALAD1-1 subjects respond differently and may be more susceptible than ALAD1-2 subjects to the ALA- mediated neurotoxic effects of lead.

Original languageEnglish (US)
Pages (from-to)15-20
Number of pages6
JournalAmerican Journal of Industrial Medicine
Volume32
Issue number1
DOIs
StatePublished - Jul 1997

Keywords

  • aminolevulinic acid
  • blood lead
  • genotype
  • lead-exposed workers
  • neurotoxin

ASJC Scopus subject areas

  • Public Health, Environmental and Occupational Health

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