慢性阻塞性肺疾的致病機轉與基因多形態間有很複雜之相關性，如GST (穀胱甘肽-S-轉移酶)和mEPH (微粒體環氧化物水解酶)。但是目前有關GST和mEPH與慢性阻塞性肺疾之間的基因多型性差異研究結果皆不一致，而這些差異都有可能是因為種族、性別...等因素造成的。而這項實驗的目的主要就是想要來確認並證實在男性患者間慢性阻塞性肺疾與mEPH、GSTP1以及GSTM1基因多型性之差異。
本實驗蒐集來自成大醫院149位慢性阻塞性肺疾患者以及125位前往家庭醫師科健檢的健康對照組，簽署同意書後分別各抽取約8 ml血液進行DNA抽取、PCR以及RFLP試驗後，所得結果再進行SPSS統計分析。所有受試者皆為年過40歲以上，且曾經或目前尚在抽菸(抽菸史須大於10 pack-years)的男性。
慢性阻塞性肺疾男性患者與Microsomal epoxide hydrolase (mEPH)之基因多型性差異研究中發現mEPH的His113/His113 (mutant)基因型得到慢性阻塞性肺病的危險機率是His113/ Tyr113 (heterogenous)和Tyr113/Tyr113 (wild type)的1.84倍 (95 %信賴區間 1.03~3.27；P= 0.038)，有統計上的顯著意義。而慢性阻塞性肺疾男性患者與GSTP1以及GSTM1之基因多型性差異研究中發現完全沒有統計上的顯著差異。
在慢性阻塞性肺疾的男性抽菸患者中mEPH exon3的His113/His113 (mutant)基因型是一個顯著的危險因素，而GSTP1以及GSTM1則無。

Genetic association studies have implicated a variety of gene in COPD pathogenesis, such as GST (Glutathione-S-transferase) and mEPH (microsomal epoxide hydrolase) for COPD patients in Taiwan. The current problem in studies of genetic polymorphism of GST and mEPH in COPD is the different results from various studies. These may occur because of the phenotype definitions, sex or ethnic difference. The aim of this study is to confirm and advance our knowledge of the role of this genetic variation in COPD.
The genotypes of 149 patients with COPD and 125 control subjects were evaluated by polymerase chain reaction and followed by restriction fragment length polymorphism analysis of the mEPH and GST (GST-P1 and M1) genes. All subjects were men over 40 years-old who smoked.
The mEPH 113 (His113/His113) mutant homozygote had a strong association with COPD (OR 1.84, 95%CI: 1.03-3.27), patients with the His113 mutant homozygote was increased in COPD patients as compared with the control group (43.6% [65/149] vs. 30.4% [38/125]; p= 0.024). No significant difference of GST genetic variation between COPD and control group was noted.
mEPH 113 mutant homozygote but not GST gene polymorphism was a significant risk factor in susceptibility to COPD in male smokers.

國立中山大學研究生學位論文審定書 i
致 謝 ii
摘 要 iii
Abstract iv
目錄 v
圖目錄 viii
表目錄 viiii
附錄 ix
縮 寫 x
第一章 前言 1
第一節 研究背景 1
第二節 研究目的 5
第二章 研究材料與方法 6
第一節 研究對象選取 6
第二節 研究材料與方法 6
3-2-1 DNA萃取方法 7
3-2-2 聚合酶連鎖反應 (Polymerase Chain Reaction) 7
3-2-3限制片段多樣性分析(Restriction Fragment Length Polymorphism) 8
3-2-4 膠體電泳分析 9
第三節 統計方法 10
第三章 結果 11
第四章 討論 13
第一節 研究成果與文獻探討 (mEPH) 13
第二節 研究成果與文獻探討 (GSTP1) 15
第三節 研究成果與文獻探討 (GSTM1) 16
第五章 結論 17
第一節 研究限制 17
第二節 研究總結 17
第三節 未來展望 18
第六章 參考文獻 19
圖 23
表 26
附錄 31
自述 41

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