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

Am J Ind Med. 1997 Jul;32(1):15-20. doi: 10.1002/(sici)1097-0274(199707)32:1<15::aid-ajim2>;2-q.


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, 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 ALADI (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.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adult
  • Aminolevulinic Acid / blood*
  • Genotype
  • Humans
  • Korea
  • Lead*
  • Male
  • Middle Aged
  • Occupational Exposure*
  • Porphobilinogen Synthase / genetics*


  • Lead
  • Aminolevulinic Acid
  • Porphobilinogen Synthase