Interaction of the delta-aminolevulinic acid dehydratase polymorphism and lead burden on cognitive function: the VA normative aging study

J Occup Environ Med. 2008 Sep;50(9):1053-61. doi: 10.1097/JOM.0b013e3181792463.


Objective: We evaluated the modifying influence of a delta-aminolevulinic acid dehydratase (ALAD) polymorphism on the relation between lead burden and cognition among older men.

Methods: Information on ALAD genotype, lead measurements, potential confounders, and cognitive testing was collected from 982 participants. For each cognitive test and lead biomarker, we fit separate multiple linear regression models, which included an interaction term for ALAD genotype and the lead biomarker and adjusted for potential confounders.

Results: With higher levels of tibia lead, ALAD 1-2/2-2 carriers exhibited worse performance on a spatial copying test in comparison with ALAD 1-1 carriers (P interaction = 0.03). However, there was no consistent pattern of an ALAD genotype-lead interaction for the other tests.

Conclusions: The results provide some evidence that ALAD genotype may modify the relation between lead and cognition among older men with low lead burden. However, future work in this area is needed to confirm these suggestive findings.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Aging
  • Body Burden
  • Bone and Bones
  • Cognition Disorders / complications
  • Cognition Disorders / enzymology*
  • Cognition Disorders / genetics
  • Enzymes / genetics*
  • Humans
  • Lead / adverse effects*
  • Lead / analysis
  • Lead / pharmacokinetics
  • Lead Poisoning / psychology*
  • Male
  • Massachusetts
  • Middle Aged
  • Polymorphism, Genetic*
  • Porphobilinogen Synthase / genetics*
  • United States
  • United States Department of Veterans Affairs
  • Young Adult


  • Enzymes
  • Lead
  • Porphobilinogen Synthase