臺灣博碩士論文加值系統

研究背景：長期暴露於金屬或有毒元素會引發許多疾病。鉛、鎘、砷是環境中常見毒性物質，硒、鈷、銅、鋅是人體必需微量元素，但超過正常血中濃度時也可能對人體造成傷害。這些多重元素之間的交互作用相當複雜，至今仍不清楚。毒性元素對健康造成負面影響的機轉之一是透過發炎反應。腫瘤壞死因子-α(TNF-α)是發炎反應中的重要調節因子，目前已發現人體TNF-α基因啟動子單一核&;#33527;酸基因多型性。本研究的目標是分析TNF-α基因多型性與血中多重元素交互作用對於血清TNF-α值的影響。
研究方法：從高雄醫學大學附設醫院收集462位金屬工業工人年度健康檢查的血液樣本，分析其生化數據、TNF-α基因型、血中七種元素濃度、血清TNF-α值，以混合效果模型分析其間交互作用。
結果：元素間交互作用以銅-鋅和鉛-鋅為最高，七種元素皆與血清TNF-α值呈正相關且受TNF-α基因多型性調控。
結論：TNF-α基因多型性與多重元素的交互作用會影響血清TNF-α值，我們建議具易感性基因型而有較高血清TNF-α值的工人必須小心金屬毒性。

Background: Chronic exposure to metals or toxic elements may contribute to many diseases. Lead (Pb), cadmium (Cd), and arsenic (As) were reported to be toxic agents in the environment. Selenium (Se), cobalt (Co), copper (Cu), and zinc (Zn) are essential trace elements for human, but they may do harm to health beyond normal serum concentrations. The interactions among multiple elements are very complicated and remain unclear. One of the mechanisms of how toxic elements have negative effects on health is through inflammation. Tumor necrosis factor-α (TNF-α) is an important mediator of inflammation, and several single nucleotide polymorphisms (SNPs) have been identified in the human TNF gene promoter. The aim of our research is to analyze how TNF-α gene polymorphisms and multi-elements interaction influence serum TNF-α level.
Method: A total of 462 metal industrial workers who have received annual health examination in Kaohsiung Medical University Hospital were recruited. The blood samples were sent for biochemical analyses, TNF-α genotype analyses (-238G>A, -308G>A, -857C>T, -863C>A, -1031T>C), and measurement of blood multi-elements concentrations (Pb, Cd, As, Se, Co, Cu, Zn) and serum TNF-α level. Mixed-effect models were used for analyzing complex interactions of multi-elements and multiple TNF-α SNPs.
Result: With regard to the interactive effects between elements, Cu-Zn and Pb-Zn have the highest Pearson correlation coefficients (0.51 and 0.49, respectively). Seven elements in our research have positive correlation with serum TNF-α level, and the effects may be modified by TNF-α gene polymorphisms.
Conclusion: Interactions between TNF-α gene polymorphisms and multi-elements may influence serum TNF-α level. We suggest that the workers with susceptible TNF-α genotypes which may induce higher serum TNF-α level should pay more attention to metal toxicity.

中文摘要 .............................................1
ABSTRACT .............................................2
INDEX ................................................4
INTRODUCTION .........................................6
MATERIAL AND METHODS .................................8
RESULTS ..............................................12
TABLES ...............................................15
DISCUSSUION ..........................................23
CONCLUSION ...........................................26
REFERENCE ............................................27

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