臺灣博碩士論文加值系統

中文摘要
　　研究背景：過去研究顯示細懸浮微粒可能會造成心血管疾病等不良健康效應，但暴露於細懸浮微粒與DNA甲基化和DNA羥甲基化的生物機轉目前尚未明確。
　　研究目的：探討陸軍航空部隊地勤維修人員暴露於細懸浮微粒與DNA甲基化之相關性，希望藉此生物標記，能在不久將來協助建立疾病早期預測機制與職業傷害防範系統。
　　材料與方法：本研究採用縱貫式研究，以陸航地勤維修人員為研究對象，研究期間為一年且每隔二至三個月追蹤一次，共計召募人數為68位。使用個人PM2.5空氣採樣設備進行8小時個人空氣採樣；工作後進行體檢收集，並測量血液中白血球DNA之5-甲基胞嘧啶（5mC）與5-羥甲基胞嘧啶（5hmC）的百分比。統計分析使用迴歸分析與廣義估計方程式進行相關性分析。
　　結果：使用廣義估計方程式分析四次追蹤，當分析範圍為全體受試人員時，無論在校正前後，（校正年齡、性別、BMI、吸菸、溫度、濕度、追蹤次數），均可發現細懸浮微粒暴露濃度增加時，DNA甲基化（5mC%）會隨之下降，且達到顯著（β=-0.148，P=0.024）。
結論：暴露於環境中細懸浮微粒會造成整體DNA甲基化之下降。未來仍需更多的大型研究來證實這些關聯性。
關鍵字：細懸浮微粒、DNA甲基化、DNA羥甲基化

Abstract
Background: Previous studies have reported that PM2.5 could cause many adverse health effects including cardiovascular diseases. However, information regarding the associations between personal exposure to fine particulate matter and DNA methylation is still limited.
Objectives: To investigate the relationships between fine particles exposure and DNA methylation among the helicopter repairers in Army.
Methods: We carried out a repeated measurement study among the helicopter repairers in Army. A total of 68 participants were recruited and followed up every two to three months between July 2016 and June 2017. We used PM2.5 personal sampler to collect breathing-zone particulate samples. After work shift, blood sample were collected and analyzed for DNA methylation and DNA hydroxymethylation. Multiple linear regression and generalized estimation equations（GEE）were applied to examine these associations after adjustment for covariates.
Results: We found that personal exposure to PM2.5 was significantly associated with a decreased DNA methylation level in blood samples after adjustment for potential covariates (β=-0.148，p =0.024).
Conclusions: Exposure to fine particles could influence the levels of global DNA methylation. Large-scale studies in the future are required to confirm these associations and elaborate the possible mechanism.

Key words: Fine particulate matter, DNA methylation, DNA hydroxymethylation.

目錄
第一章 緒論 1
第一節、研究背景及重要性 1
第二節、研究目的 5
第二章 文獻探討 6
第一節、陸航直升機維修員所暴露之細懸浮微粒污染 6
第二節、表觀遺傳學與DNA甲基化指標 12
第三節、細懸浮微粒暴露下之DNA甲基化相關研究 19
第三章 材料與方法 30
第一節、研究設計與架構 30
第二節、研究假設 32
第三節、研究工具 33
第四節、實驗流程 35
第五節、實驗品質管制 41
第六節、資料處理與統計方法 44
第四章 結果 46
第一節、基本人口學特徵 46
第二節、研究對象細懸浮微粒暴露情形之描述與檢定 47
第三節、甲基化與羥甲基化標記之描述及檢定 53
第四節、細懸浮微粒與DNA甲基化、DNA羥甲基化之斯皮爾曼相關性 58
第五節、研究對象細懸浮微粒暴露與甲基化、羥甲基化之橫斷分析 60
第六節、研究對象細懸浮微粒暴露與甲基化、羥甲基化之縱貫分析 66
第五章 討論 69
第一節、細懸浮微粒暴露濃度探討 69
第二節、細懸浮微粒暴露對DNA甲基化、DNA羥甲基化影響探討 72
第三節、細懸浮微粒暴露之細胞生物學、實驗動物探討 76
第四節、研究限制與優點 78
第六章 結論與建議 79
第一節、結論 79
第二節、建議 79
參考文獻 80

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