Delta-aminolevulinic acid dehydratase (ALAD) polymorphism and susceptibility of workers exposed to inorganic lead and its effects on neurobehavioral functions

Neurotoxicology. 2004 Dec;25(6):1041-7. doi: 10.1016/j.neuro.2004.01.010.


We carried out a cross-sectional study on a group of male workers to determine the frequency of delta-aminolevulinic acid dehydratase (ALAD) polymorphisms among Chinese, Malays and Indians workers who were exposed to low to medium levels of inorganic lead. Also, the association between ALAD1 and ALAD2 genotypes and neurobehavioral functions among these workers were investigated. A total of 120 male workers were studied. Blood and urine were collected for each worker to determine the ALAD genotypes, blood lead levels, ALAD, and urinary delta-aminolevulinic acid (ALAU). ALAD1-1 was the predominant genotype for all three ethnic groups while ALAD2-2 was the rarest. The distribution of ALAD1-2 was higher among Malays (16.7%) and Indians (14.3%), compared to Chinese (3.6%). Selected tests from the World Health Organization Neurobehavioral Core Test Battery (WHO-NCTB) were used. Although workers in the ALAD1-1 and ALAD1-2/2-2 groups had comparable blood lead levels, the 106 workers with ALAD1-1 genotypes have significantly higher urinary ALA and significantly poorer neurobehavioral scores involving motor dexterity compared with those who have ALAD1-2/2-2 genotypes (13 workers). It is postulated that the ALAD2 allele may exert protective measures against the neurotoxic effects of lead. Further study involving a larger cohort of workers with the ALAD2 allele would be needed to confirm this hypothesis.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Chemical Industry* / statistics & numerical data
  • Cross-Sectional Studies
  • Gene Frequency / drug effects
  • Gene Frequency / genetics
  • Humans
  • Lead / blood
  • Lead / toxicity*
  • Male
  • Middle Aged
  • Occupational Exposure / adverse effects*
  • Occupational Exposure / statistics & numerical data
  • Polymorphism, Genetic / drug effects*
  • Polymorphism, Genetic / genetics
  • Porphobilinogen Synthase / blood
  • Porphobilinogen Synthase / genetics*
  • Psychomotor Disorders / blood
  • Psychomotor Disorders / chemically induced*
  • Psychomotor Disorders / genetics


  • Lead
  • Porphobilinogen Synthase