Modifying effects of δ-Aminolevulinate dehydratase polymorphism on blood lead levels and ALAD activity

Lead is an environmental hazard with great public health concern and has been known to inhibit delta-aminolevulinate dehydratase (ALAD) activity involved in the heme biosynthetic pathway. The study aimed to investigate the influence of ALAD polymorphism (G177C) on retention of Pb-B levels and ALAD activity on occupationally exposed lead workers. In the present study, we enrolled 561 lead exposed and 317 non-occupationally exposed subjects and performed a comprehensive analysis of Pb-B levels along with ALAD activity and genotyping. The frequency of ALAD variants observed in the total subjects (n = 878) was 70.04% for ALAD 1-1, 27.44% for heterozygous ALAD 1-2 and 2.5% for homozygous mutant ALAD 2-2. Our study revealed that ALAD 1-2 carriers presented higher Pb-B levels compared to wild type ALAD 1-1 carriers. Further, a significant difference was observed in the activity of ALAD between ALAD 1-2/ 2-2 and ALAD 1-1 carriers of non-occupationally exposed group indicating that the polymorphic nature of the enzyme may contribute to altered activity of ALAD irrespective of lead exposure. Hence, ALAD 2 allele might contribute to increased susceptibility to high Pb-B retention, and genotyping of ALAD in lead exposed subjects might be used as a prediction marker to impede tissue/organ damage due to lead toxicity.