TY - JOUR
T1 - Influence of VDR and HFE polymorphisms on blood lead levels of occupationally exposed workers
AU - Mani, Monica Shirley
AU - Puranik, Amitha
AU - Kabekkodu, Shama Prasada
AU - Joshi, Manjunath B.
AU - Dsouza, Herman Sunil
N1 - Funding Information:
The authors acknowledge TIFAC-CORE, Government of India and Manipal Academy of Higher Education for the infrastructure. We thank Prof. K Satyamoorthy, Director, Manipal School of Life Sciences, Manipal Academy of Higher Education, Manipal, India, for the valuable support and encouragement. We are grateful to the participants of the study for allowing us to collect their blood samples. We also thank the phlebotomists of Kasturba Medical College, Attavara, Mangalore for assisting us in the blood sample collection. We would also like to thank Mr. A R. Kini (B.Sc. DMLT) for analyzing the complete hematogram, total serum protein, and SGOT/SGPT levels. Dr. Monica Shirley Mani was provided with a fellowship from Dr. T.M.A. Pai Foundation, Manipal Academy of Higher Education (131700103) and Directorate of Minorities (Award no. DOM/FELLOWSHIP/CR-84/2017-18).
Publisher Copyright:
© The Author(s) 2020.
Copyright:
Copyright 2020 Elsevier B.V., All rights reserved.
PY - 2021/1/1
Y1 - 2021/1/1
N2 - Lead is a ubiquitous heavy metal toxin of significant public health concern. Every individual varies in their response to lead’s toxic effects due to underlying genetic variations in lead metabolizing enzymes or proteins distributed in the population. Earlier studies, including our lab, have attributed the influence of ALAD (δ-Aminolevulinate dehydratase) polymorphism on blood lead retention and ALAD activity. The present study aimed to investigate the influence of VDR (Vitamin D receptor) and HFE (Hemochromatosis) polymorphisms in modulating blood lead levels (BLLs) of occupationally exposed workers. 164 lead-exposed subjects involved in lead alloy manufacturing and battery breaking and recycling processes and 160 unexposed controls with BLLs below 10 µg/dL recruited in the study. Blood lead levels, along with a battery of biochemical assays and genotyping, were performed. Regression analysis revealed a negative influence of BLLs on ALAD activity (p < 0.0001) and a positive influence on smokeless tobacco use (p < 0.001) in lead-exposed subjects. A predicted haplotype of the three VDR polymorphisms computed from genotyping data revealed that T-A-A haplotype increased the BLLs by 0.93 units (p ≤ 0.05) and C-C-A haplotype decreased the BLLs by 7.25 units (p ≤ 0.05). Further analysis revealed that the wild-type CC genotype of HFE H63D presented a higher median BLL, indicating that variant C allele may have a role in increasing the concentration of lead. Hence, the polymorphism of genes associated with lead metabolism might aid in predicting genetic predisposition to lead and its associated effects.
AB - Lead is a ubiquitous heavy metal toxin of significant public health concern. Every individual varies in their response to lead’s toxic effects due to underlying genetic variations in lead metabolizing enzymes or proteins distributed in the population. Earlier studies, including our lab, have attributed the influence of ALAD (δ-Aminolevulinate dehydratase) polymorphism on blood lead retention and ALAD activity. The present study aimed to investigate the influence of VDR (Vitamin D receptor) and HFE (Hemochromatosis) polymorphisms in modulating blood lead levels (BLLs) of occupationally exposed workers. 164 lead-exposed subjects involved in lead alloy manufacturing and battery breaking and recycling processes and 160 unexposed controls with BLLs below 10 µg/dL recruited in the study. Blood lead levels, along with a battery of biochemical assays and genotyping, were performed. Regression analysis revealed a negative influence of BLLs on ALAD activity (p < 0.0001) and a positive influence on smokeless tobacco use (p < 0.001) in lead-exposed subjects. A predicted haplotype of the three VDR polymorphisms computed from genotyping data revealed that T-A-A haplotype increased the BLLs by 0.93 units (p ≤ 0.05) and C-C-A haplotype decreased the BLLs by 7.25 units (p ≤ 0.05). Further analysis revealed that the wild-type CC genotype of HFE H63D presented a higher median BLL, indicating that variant C allele may have a role in increasing the concentration of lead. Hence, the polymorphism of genes associated with lead metabolism might aid in predicting genetic predisposition to lead and its associated effects.
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U2 - 10.1177/0960327120975451
DO - 10.1177/0960327120975451
M3 - Article
AN - SCOPUS:85096512399
SN - 0960-3271
JO - Human and Experimental Toxicology
JF - Human and Experimental Toxicology
ER -
