Genetic susceptibility of δ-ALAD associated with lead (Pb) intoxication: sources of exposure, preventive measures, and treatment interventions

Abstract

Delta-aminolevulinic acid dehydratase (δ-ALAD) is involved in the synthesis of haem and exhibits a polymorphic nature. δ-ALAD polymorphism produces two alleles, namely δ-ALAD-1 and δ-ALAD-2, which in turn produce three different phenotypes, namely δ-ALAD1-1, δ-ALAD1-2, and δ-ALAD2-2. δ-ALAD gene is more susceptible to lead (Pb) toxicity than any other genes. Its genotype and phenotype frequencies change with respect to different geographical areas and extent of Pb exposure. The δ-ALAD-2 allele dominancy is linked with high concentration of lead in the body. It has also been thought that the δ-ALAD-2 allele can provoke Pb toxicity by producing a protein that binds more tightly with Pb than δ-ALAD-1 protein. However, few evidences suggest that δ-ALAD-2 may reduce harmful effects by increasing excretion of Pb from the body, thus producing its unavailability towards pathophysiologic alterations. However, the recent evidences have supported that the individuals who are heterozygote for the δ-ALAD-1 allele may be associated with a higher risk of long-term Pb toxicity. In this regard, the individuals who are exposed at occupational levels are among the most frequent study population. The main objective of our study was to explore the gene susceptibility associated with Pb poisoning. Moreover, this study also summarizes various sources of Pb exposure and thereafter outlined multiple strategies to minimize the Pb toxicity in order to save the exposed residential communities.

Keywords: Exposure of lead; Lead toxicity; Polymorphism; Preventive measure; Therapeutic interventions; δ-ALAD.