Influence of VDR and HFE polymorphisms on blood lead levels of occupationally exposed workers

• Published in: Human & experimental toxicology Vol. 40; no. 6; pp. 897 - 914
• Main Authors: Mani, Monica Shirley, Puranik, Amitha, Kabekkodu, Shama Prasada, Joshi, Manjunath B, Dsouza, Herman Sunil
• Format: Journal Article
• Language: English
• Published: London, England SAGE Publications 01.06.2021; Sage Publications Ltd
• Subjects: Blood; Blood levels; Dehydration; Exposure; Gene polymorphism; Genetic diversity; Genotyping; Haplotypes; Heavy metals; Hemochromatosis; Lead base alloys; Lead content; Lead poisoning; Metabolism; Occupational exposure; Polymorphism; Population studies; Public health; Regression analysis; Tobacco; Toxicity; Toxins; Vitamin D; Vitamin D receptors; haplotype; SNP; VDR; HFE; Lead; blood lead levels; genotype
• ISSN: 0960-3271; 1477-0903
• DOI: 10.1177/0960327120975451

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.