From the aDepartment of Environmental and Occupational Medicine, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan, Republic of China; bDepartment of Family Medicine, Pingtung Christian Hospital, Pingtung, Taiwan, Republic of China; cProgram for Clinical Pharmacogenomics and Pharmacoproteomics, School of Pharmacy, Taipei Medical University, Taipei, Taiwan, Republic of China; and dDepartment of Public Health, Kaohsiung Medical University, Kaohsiung, Taiwan, Republic of China.
Epidemiology. 2017 Oct;28 Suppl 1:S113-S120. doi: 10.1097/EDE.0000000000000738.
Lead (Pb), cadmium (Cd), and arsenic (As) could cause health issues through oxidative stress that is indicated in the elevated tumor necrosis factor-alpha (TNF-α). However, some of the essential elements-selenium (Se), zinc (Zn), cobalt (Co), and copper (Cu)-are cofactors or structural components of antioxidant enzymes. It is suggested that single-nucleotide polymorphisms (SNPs) in the TNF-α gene have different TNF-α responses. This study aims to evaluate the effect of serum TNF-α levels through the interactions between toxic metals and essential elements and how the interactions between the toxic metals and TNF-α SNPs (-1031 T > C, -863 C > A, -857 C > T, -308 G > A, -238 G > A) influence serum TNF-α levels.
Blood samples were collected from 455 workers who carried out annual health examinations and multielements determined by inductively coupled plasma mass spectrometry (ICP-MS). TNF-α levels were detected by enzyme-linked immunosorbent assay (ELISA). TNF-α promoter SNPs were analyzed by specific primer probes using real-time polymerase chain reaction (PCR) methods.
Increasing blood Pb, Cd, and As levels were associated with elevated TNF-α levels. The interaction between Pb and Cu decreased TNF-α levels and so did the interaction between Cd and Se. In the interaction between Pb and SNPs, individuals with AA/AG (-308 G > A) and AA/AG (-238 G > A) had higher serum TNF-α levels. However, lower TNF-α levels were noted in those individuals with AA/CA (-863 C > A). In the interaction between As and SNPs, workers with AA/AG (-238 G > A) had synergic effect with As and induced higher serum TNF-α levels.
Blood Cu and Se were antagonists of toxic metals (Pb, As, and Cd) through lower serum TNF-α levels. Variant types of TNF-α SNPs (-308 G > A, -238 G > A) and wild type of -863 CC would be more susceptible to toxic metals.
铅（Pb）、镉（Cd）和砷（As）可通过升高的肿瘤坏死因子-α（TNF-α）引起氧化应激，从而导致健康问题。然而，一些必需元素-硒（Se）、锌（Zn）、钴（Co）和铜（Cu）-是抗氧化酶的辅助因子或结构成分。有研究表明，肿瘤坏死因子-α（TNF-α）基因中的单核苷酸多态性（SNPs）会导致不同的 TNF-α 反应。本研究旨在通过有毒金属与必需元素之间的相互作用来评估血清 TNF-α 水平的变化，并研究有毒金属与 TNF-α SNPs（-1031T>C、-863C>A、-857C>T、-308G>A、-238G>A）之间的相互作用如何影响血清 TNF-α 水平。
从进行年度健康检查的 455 名工人中采集血样，采用电感耦合等离子体质谱法（ICP-MS）测定多种元素。采用酶联免疫吸附试验（ELISA）检测 TNF-α 水平。采用实时聚合酶链反应（PCR）方法，用特定的引物探针分析 TNF-α 启动子 SNPs。
随着血液 Pb、Cd 和 As 水平的升高，TNF-α 水平也随之升高。Pb 与 Cu 的相互作用降低了 TNF-α 水平，而 Cd 与 Se 的相互作用也是如此。在 Pb 与 SNPs 的相互作用中，具有 AA/AG（-308G>A）和 AA/AG（-238G>A）基因型的个体血清 TNF-α 水平较高。然而，具有 AA/CA（-863C>A）基因型的个体 TNF-α 水平较低。在 As 与 SNPs 的相互作用中，具有 AA/AG（-238G>A）基因型的工人与 As 存在协同作用，导致血清 TNF-α 水平升高。
血液 Cu 和 Se 是通过降低血清 TNF-α 水平拮抗有毒金属（Pb、As 和 Cd）的。TNF-α SNPs（-308G>A、-238G>A）的变异型和野生型-863CC 对有毒金属更为敏感。
