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

Monica Shirley Mani, Vidya Kunnathully, Chaitra Rao, Shama Prasada Kabekkodu, Manjunath B. Joshi, Herman Sunil D'Souza

Research output: Contribution to journalArticle

3 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)351-356
Number of pages6
JournalToxicology Letters
Volume295
DOIs
Publication statusPublished - 01-10-2018

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Hydro-Lyases
Polymorphism
Blood
Lead
Porphobilinogen Synthase
Biosynthetic Pathways
Public health

All Science Journal Classification (ASJC) codes

  • Toxicology

Cite this

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title = "Modifying effects of δ-Aminolevulinate dehydratase polymorphism on blood lead levels and ALAD activity",
abstract = "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.",
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Modifying effects of δ-Aminolevulinate dehydratase polymorphism on blood lead levels and ALAD activity. / Mani, Monica Shirley; Kunnathully, Vidya; Rao, Chaitra; Kabekkodu, Shama Prasada; Joshi, Manjunath B.; D'Souza, Herman Sunil.

In: Toxicology Letters, Vol. 295, 01.10.2018, p. 351-356.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Modifying effects of δ-Aminolevulinate dehydratase polymorphism on blood lead levels and ALAD activity

AU - Mani, Monica Shirley

AU - Kunnathully, Vidya

AU - Rao, Chaitra

AU - Kabekkodu, Shama Prasada

AU - Joshi, Manjunath B.

AU - D'Souza, Herman Sunil

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