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Modifying effects of δ-Aminolevulinate dehydratase polymorphism on blood lead levels and ALAD activity.
Toxicol Lett 2018; 295:351-356TL

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.

Authors+Show Affiliations

Department of Radiobiology and Toxicology, School of Life Sciences, Manipal Academy of Higher Education, Manipal, Karnataka, India.Department of Radiobiology and Toxicology, School of Life Sciences, Manipal Academy of Higher Education, Manipal, Karnataka, India.Department of Radiobiology and Toxicology, School of Life Sciences, Manipal Academy of Higher Education, Manipal, Karnataka, India.Department of Cellular and Molecular Biology, School of Life Sciences, Manipal Academy of Higher Education, Manipal, Karnataka, India.Department of Ageing, School of Life Sciences, Manipal Academy of Higher Education, Manipal, Karnataka, India.Department of Radiobiology and Toxicology, School of Life Sciences, Manipal Academy of Higher Education, Manipal, Karnataka, India. Electronic address: hs.dsouza@manipal.edu.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

30025905

Citation

Mani, Monica Shirley, et al. "Modifying Effects of δ-Aminolevulinate Dehydratase Polymorphism On Blood Lead Levels and ALAD Activity." Toxicology Letters, vol. 295, 2018, pp. 351-356.
Mani MS, Kunnathully V, Rao C, et al. Modifying effects of δ-Aminolevulinate dehydratase polymorphism on blood lead levels and ALAD activity. Toxicol Lett. 2018;295:351-356.
Mani, M. S., Kunnathully, V., Rao, C., Kabekkodu, S. P., Joshi, M. B., & D'Souza, H. S. (2018). Modifying effects of δ-Aminolevulinate dehydratase polymorphism on blood lead levels and ALAD activity. Toxicology Letters, 295, pp. 351-356. doi:10.1016/j.toxlet.2018.07.014.
Mani MS, et al. Modifying Effects of δ-Aminolevulinate Dehydratase Polymorphism On Blood Lead Levels and ALAD Activity. Toxicol Lett. 2018 Oct 1;295:351-356. PubMed PMID: 30025905.
* Article titles in AMA citation format should be in sentence-case
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, Y1 - 2018/07/17/ PY - 2018/02/22/received PY - 2018/06/07/revised PY - 2018/07/16/accepted PY - 2018/7/22/pubmed PY - 2018/8/30/medline PY - 2018/7/21/entrez KW - ALAD KW - Blood lead level KW - Lead KW - Polymorphism SP - 351 EP - 356 JF - Toxicology letters JO - Toxicol. Lett. VL - 295 N2 - 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. SN - 1879-3169 UR - https://www.unboundmedicine.com/medline/citation/30025905/Modifying_effects_of_δ_Aminolevulinate_dehydratase_polymorphism_on_blood_lead_levels_and_ALAD_activity_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0378-4274(18)31501-7 DB - PRIME DP - Unbound Medicine ER -