Abstract
Despite the phasing out of leaded gasoline, lead-based paint and leaded plumbing, lead (Pb) remains a public health risk. Toxicity of Pb occurs primarily due to its inhibition of key enzymes in biosynthesis of heme, a compound required for oxygen biding in bloodstream. One of these enzymes is δ-aminolevulinic acid dehydratase (ALAD), the main binding ligand for Pb in erythrocytes. The ALAD enzyme is encoded by the ALAD gene. This gene has two co-dominant alleles (ALAD1 and ALAD2), three genotypes (ALAD1-1, ALAD1-2 and ALAD2-2) and dozens of detected single nucleotide polymorphisms. The G to C transversion in nucleotide 177 in ALAD2 is the difference between ALAD1 and ALAD2 genotypes. This mutation changed the enzyme activity and is the reason it is suggested that individuals with the less common ALAD2 allele tend to experience a greater susceptibility to Pb toxicity than individuals with ALAD1. However, the association of ALAD polymorphism with Pb toxicity remained inconclusive when Pb exposure resulted in blood Pb level < 10 μg/dL, though numerous studies showed that blood Pb level > 10 μg/dL compromised heme synthesis, with the ALAD activity inversely correlated with blood Pb. This review suggests that use of specific combinations of ALAD single nucleotide polymorphisms as biomarkers for susceptibility to Pb exposure and toxicity might contribute to a better understanding of Pb association with ALAD polymorphism. Based on evidence reviewed herein, the current blood lead reference value of 3.5 μg/dL should be further reduced to 0 μg/dL.