Toxic Metals Increase Serum Tumor Necrosis Factor-α Levels, Modified by Essential Elements and Different Types of Tumor Necrosis Factor-α Promoter Single-nucleotide Polymorphisms

Background: 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-alpha). 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-alpha gene have different TNF-alpha responses. This study aims to evaluate the effect of serum TNF-alpha levels through the interactions between toxic metals and essential elements and how the interactions between the toxic metals and TNF-alpha SNPs (-1031 T > C, -863 C > A, -857 C > T, -308 G > A, -238 G > A) influence serum TNF-alpha levels. Methods: 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-alpha levels were detected by enzyme-linked immunosorbent assay (ELISA). TNF-alpha promoter SNPs were analyzed by specific primer probes using real-time polymerase chain reaction (PCR) methods. Results: Increasing blood Pb, Cd, and As levels were associated with elevated TNF-alpha levels. The interaction between Pb and Cu decreased TNF-alpha 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-alpha levels. However, lower TNF-alpha 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-alpha levels. Conclusions: Blood Cu and Se were antagonists of toxic metals (Pb, As, and Cd) through lower serum TNF-alpha levels. Variant types of TNF-alpha SNPs (-308 G > A, -238 G > A) and wild type of -863 CC would be more susceptible to toxic metals.