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研究生:余曉筌
研究生(外文):Yu Hsiao-Chang
論文名稱:GSTT1,mEH基因多形性與環氧乙烷血紅素鍵結物之相關研究
論文名稱(外文):Effect on N-2-hydroxyethyl valine hemoglobin adducts of glutathione S-transferase T1 genotype, and gender in cigarette smokers
指導教授:鄭尊仁鄭尊仁引用關係吳焜裕吳焜裕引用關係
指導教授(外文):Cheng Tsun-JenWu Kuen-Yuh
學位類別:碩士
校院名稱:國立臺灣大學
系所名稱:職業醫學與工業衛生研究所
學門:醫藥衛生學門
學類:公共衛生學類
論文出版年:2001
畢業學年度:89
語文別:中文
論文頁數:66
中文關鍵詞:環氧乙烷基因多形性性別血紅素鍵結物抽菸
外文關鍵詞:ethylene oxideGSTT1microsomal epoxide hydrolasegenderhemoglobin adductscigarette smoking
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過去的研究顯示環氧乙烷血紅素鍵結物 HEV (N-2-hydroxyethyl valine)可用來當作人體的環氧乙烷暴露劑量指標,先前的研究發現人體HEV的濃度與抽菸有顯著的相關,並且有劑量-反應關係。有研究指出人體HEV的濃度與與GSTT1( glutathione S-transferase T1 )基因多形性有相關。除此之外,mEH( microsomal epoxide hydrolase )在環氧乙烷的代謝上可能扮演重要的角色。本研究主要想探討抽菸者體內的環氧乙烷血紅素鍵結物是否與GSTT1,mEH等基因多形性有相關。
研究對象為台中市某捐血站150位自願捐血者,利用問卷調查的方式收集抽菸習慣,潛在二手菸暴露及其他生活習慣(包括喝酒,喝咖啡,喝茶等)等基本資料。環氧乙烷血紅素鍵結物是利用modified Edman degradation method測定,基因多形性分析係利用聚合脢鍊鎖反應-限制片段長度多形性分析(PCR-RFLP)。
結果顯示,每天抽菸支數在男性與女性皆與環氧乙烷血紅素鍵結物增加有顯著相關(p<0.01)。在男性,每天抽菸支數和GSTT1基因型對於血紅素鍵結物增加有顯著交互作用(p=0.03)。在女性雖然有同樣的趨勢但未達統計上顯著的差別(p=0.08)。有趣的是,控制了抽菸以及GSTT1基因型後女性比男性仍有較高的HEV濃度(p=0.05)。但mEH基因型與體內HEV濃度並無相關。
本研究進一步確認過去有關GSTT1 無效基因型會增加抽菸者體內HEV濃度的研究。除此之外,若使用HEV當作人體環氧乙烷暴露劑量指標時,應該考慮GSTT1基因型以及性別兩個因子。

The presence of ethylene oxide adduct, N-2-hydroxyethyl valine (HEV), had been used to monitor human exposure to cigarette smoke. In the previous study, we have demonstrated that the HEV levels increased with the amount of cigarette smoking. Glutathione S-transferase T1 (GSTT1) has been reported to be associated with HEV level in cigarette smokers. Additionally, microsomal epoxide hydrolase (mEH) is also indicated in the metabolism of ethylene oxide (EO). To further investigate the role of metabolic traits on HEV level, we study the relationship of GSTT1, and mEH genotypes with HEV caused by cigarette smoke.
A total of 150 volunteers were recruited at a blood donation station in Taichung City, Taiwan. Each volunteer was administered with a standardized questionnaire to obtain information including demographic data, smoking habits, and potential confounders. HEV was analyzed with a modified Edman degradation method, and the genotypes of GSTT1 and mEH were analyzed by polymoerase chain reaction-restriction fragment length polymorphism (PCR-RFLP).
The result showed that daily amount of cigarette smoking was significantly associated with HEV level (p < 0.01) in both males and females. In males, there was an interaction between GSTT1-genotype and daily cigarette smoking on HEV level (p = 0.03), but the difference did not reach a statistical significance in females (p = 0.08). Interestingly, female had higher HEV than males after adjusting the cigarette smoking and GSTT1 (p = 0.05). However, mEH genotype was not associated with HEV level.
Our results confirmed previous studies that HEV levels increase in cigarette smokers with GSTT1-null genotype. Further, the effect of gender on HEV need to be considered when HEV is used as a dosimeter.

中文摘要I
英文摘要II
目錄III
表目錄IV
圖目錄V
第一章 前言1
第一節 環氧乙烷及其健康效應1
第二節 人體環氧乙烷暴露指標HEV2
第三節 研究目的3
第二章 文獻探討4
第一節 環氧乙烷的吸收,分佈與代謝4
第二節 GSTT1基因多形性在環氧乙烷代謝中扮演的角色5
第三節 mEH基因多形性在環氧乙烷代謝中扮演的角色6
第三章 材料與方法9
第一節 研究對象9
第二節 HEV測定9
第三節 基因形測定14
第四節 統計分析20
第四章 結果21
第一節 研究樣本基本資料與代謝基因型分佈21
第二節 未經調整之分層分析22
第三節 多變項一般線性迴歸模式23
第五章 討論25
參考目錄40
附錄一 問卷44
附錄二 (預計投CARCINOGENESIS)47

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