Individual susceptibility to the toxic effects induced by exposure to lead (Pb) may be affected by several variables, such as environmental factors, as well as intrinsic variations among the individuals, which are hypothetically associated to genetic differences in enzymes metabolizing the metal. Aim of the present study was to evaluate the effects of polymorphisms of glutathione (GSH)-genes related to the antioxidant status and Pb metabolism (GCLC, rs17883901 and GCLM, rs41303970) on Pb levels in blood (B-Pb) and plasma (P-Pb), as well as Pb-related effects on activity of glutathione-peroxidase (GPX) and on GSH concentrations. A cross-sectional study with 236 adults (men, >18 years old) was carried out with workers from automotive battery factories, Brazil. B-Pb and P-Pb were determined by ICP-MS; blood GPX and GSH were determined by spectrophotometry and qPCR TaqMan assays were used for genotyping. A questionnaire was applied in order to collect socio-demographic, lifestyle and time of exposure. The mean B-Pb level was 211 ± 118 μg/L and P-Pb was 6.05 ± 7.13 μg/L. GCLM are associated with changes of B-Pb and P-Pb; individuals who carry at least one polymorphic allele for GCLM gene had lower metal levels in the blood and plasma (β = -1.5; p = 0.0080; β = -0.12 and p = 0.050). In addition, individuals carrying at least one polymorphic allele for the GCLC gene had higher concentrations of GSH than the non-polymorphic ones, as a function of B-Pb (β = 0.072; p = 0.029). Significant associations were also observed with GCLC polymorphism on GSH concentrations (as a function of P-Pb), that is, polymorphic individuals tended to have higher concentrations of GSH than non-polymorphic ones (β = 0.072; p = 0.030), while those individuals who are polymorphic for GCLM had higher activities of GPX, compared to the non-variant genotype (β = 0.19; p = 0.028). Taken together, our data indicate that polymorphisms related to Pb toxicokinetics modify the metal body burden and Pb-related antioxidant effects.

中文翻译：

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与铅 (Pb) 代谢相关的基因多态性与身体金属负担和氧化应激的生物标志物有关。

个体对铅 (Pb) 暴露引起的毒性效应的易感性可能受到多种变量的影响，例如环境因素以及个体之间的内在差异，假设这些变量与代谢金属的酶的遗传差异有关。本研究的目的是评估与抗氧化状态和 Pb 代谢相关的谷胱甘肽 (GSH) 基因多态性 (GCLC, rs17883901 和 GCLM, rs41303970) 对血液 (B-Pb) 和血浆 (P -Pb)，以及 Pb 对谷胱甘肽过氧化物酶 (GPX) 活性和 GSH 浓度的影响。对 236 名成年人（男性，18 岁以上）进行了横断面研究，研究对象是巴西汽车电池工厂的工人。B-Pb和P-Pb采用ICP-MS测定；通过分光光度法测定血液 GPX 和 GSH，并使用 qPCR TaqMan 检测进行基因分型。使用问卷调查收集社会人口、生活方式和接触时间。平均 B-Pb 水平为 211 ± 118 μg/L，P-Pb 为 6.05 ± 7.13 μg/L。GCLM 与 B-Pb 和 P-Pb 的变化有关；携带至少一个 GCLM 基因多态性等位基因的个体在血液和血浆中的金属水平较低（β = -1.5；p = 0.0080；β = -0.12 和 p = 0.050）。此外，携带至少一个 GCLC 基因多态性等位基因的个体的 GSH 浓度高于非多态性个体，作为 B-Pb 的函数（β = 0.072；p = 0.029）。还观察到 GCLC 多态性对 GSH 浓度（作为 P-Pb 的函数）的显着关联，即，多态个体的 GSH 浓度往往高于非多态个体（β = 0.072；p = 0.030），而与非变异基因型相比，GCLM 多态个体的 GPX 活性更高（β = 0.19； p = 0.028）。总之，我们的数据表明与 Pb 毒代动力学相关的多态性改变了金属身体负荷和 Pb 相关的抗氧化作用。