δ‐Aminolevulinic Acid Dehydratase Isozymes and Lead Toxicitya

Abstract

ALAD is a zinc metalloenzyme whose inhibition by lead is the first and most sensitive indicator of lead exposure and whose decreased activity has been implicated in the pathogenesis of lead poisoning. This heme biosynthetic enzyme is encoded by a gene located at chromosome 9q34, which has two codominant alleles, ALAD1 and ALAD2. The occurrence of two frequent alleles for ALAD stimulated an investigation into the possible pharmacogenetic role of the enzyme polymorphism in lead poisoning. In a New York City population at high risk for lead exposure, individuals heterozygous or homozygous for the less common allele, ALAD2, had blood lead levels greater than or equal to 30 micrograms/dl more frequently than expected. These findings suggest a potential genetic susceptibility to lead poisoning in individuals with the ALAD 1-2 and 2-2 phenotypes.