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

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.

CONCEPTUAL MODEL OF LEAD METABOLISM IN THE ORGANISM OF FARM ANIMALS WITH MULTI-CHAMBER STOMACH UNDER INTAKE WITH A RATION

A conceptual model of lead metabolism in the organism of farm animals with a multi-chamber stomach under intake with a ration is presented. The input parameters are determined by the daily intake of lead from the diet and the factors that modify this process. The model includes three compartments: 1) transport of lead in the gastrointestinal tract (rumen, reticulum, omasum, abomasum, small and thick intestine); 2) distribution and accumulation of lead in organs and tissues (liver, kidneys, spleen, heart, lungs, blood, mammary gland, skin, muscle and bone tissue); 3) removal of lead from the body (urine, feces, wool, milk, fetal). The paper discusses the use of the model to assess the parameters of the transition on the trophic chain «ration–animal–food», forecasting and determining the acceptable level of lead intake with feed in order to ensure the production of environmentally safe products in the conduct of animal husbandry in conditions of contamination of agricultural land.

Lead

Children differ from adults in the relative importance of lead sources and pathways, lead metabolism, and the toxicities expressed. The central nervous system effects of lead on children seem not to be reversible. Periods of enhanced vulnerability within childhood have not consistently been identified. The period of greatest vulnerability might be endpoint specific, perhaps accounting for the failure to identify a coherent “behavioral signature” for lead toxicity. The bases for the substantial individual variability in vulnerability to lead are uncertain, although they might include genetic polymorphisms and contextual factors. The current Centers for Disease Control and Prevention screening guideline of 10 μg/dL is a risk management tool and should not be interpreted as a threshold for toxicity. No threshold has been identified, and some data are consistent with effects well below 10. Historically, most studies have concentrated on neurocognitive effects of lead, but higher exposures have recently been associated with morbidities such as antisocial behavior and delinquency. Studies of lead toxicity in experimental animal models are critical to the interpretation of nonexperimental human studies, particularly in addressing the likelihood that associations observed in the latter studies can be attributed to residual confounding. Animal models are also helpful in investigating the behavioral and neurobiological mechanisms of the functional deficits observed in lead-exposed humans. Studies of adults who have been exposed to lead are of limited use in understanding childhood lead toxicity because developmental and acquired lead exposure differ in terms of the maturity of the organs affected, the presumed mechanisms of toxicity, and the forms in which toxicities are expressed.