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.

铅是一种普遍存在的重金属毒素，具有重大的公共卫生问题。由于人群中分布的铅代谢酶或蛋白质的潜在遗传变异，每个人对铅毒性作用的反应各不相同。早期的研究，包括我们的实验室，已将ALAD（δ-氨基乙酰丙酸脱水酶）多态性对血铅保留和 ALAD 活性的影响归因于。本研究旨在调查VDR（维生素 D 受体）和HFE 的影响（血色病）调节职业暴露工人血铅水平（BLL）的多态性。该研究招募了 164 名参与铅合金制造和电池破碎和回收过程的铅暴露受试者和 160 名 BLL 低于 10 µg/dL 的未暴露对照。进行了血铅水平以及一系列生化分析和基因分型。回归分析揭示了铅暴露受试者中 BLL 对 ALAD 活性的负面影响 ( p < 0.0001) 和对无烟烟草使用的积极影响 ( p < 0.001)。根据基因分型数据计算的三个VDR多态性的预测单倍型显示，TAA 单倍型使 BLL 增加了 0.93 个单位（p≤ 0.05) 和 CCA 单倍型使 BLL 减少了 7.25 个单位 ( p ≤ 0.05)。进一步分析表明，HFE H63D的野生型 CC 基因型呈现出较高的 BLL 中位数，表明变异 C 等位基因可能在增加铅浓度方面发挥作用。因此，与铅代谢相关的基因多态性可能有助于预测铅的遗传易感性及其相关影响。