臺灣博碩士論文加值系統

砷在人體的解毒作用會與髓鞘的形成競爭甲基，導致神經傳導遲緩。本研究目的是希望能瞭解長期飲用含砷地下水是否會導致神經傳導速度減慢，以及與甲烯基四氫葉酸還原酵素(Methylenetetrahydrofolate reductase, MTHFR)基因多形性之間的相關性。研究對象從民國八十年於蘭陽盆地執行之世代追蹤研究的研究地區內，隨機選取一所國民中學，將學生基本資料和原有研究世代的井水所在地址比對，選出130名居住地址和井水所在地址相同的一、二年級學生為研究對象。研究對象的暴露資料來源，為該世代追蹤研究執行時所採地下水中測出的含砷濃度，以及問卷得知本研究之研究對象飲用地下水的年數、停喝年數，和每日喝水量。在神經傳導速度檢查部分，共檢測四條神經的運動傳導速度及三條神經的感覺傳導速度。運動傳導速度測量的神經包括手部之正中神經(median nerve)與尺神經(ulnar nerve) ，及腳部之腓神經(peroneal nerve)與脛神經(tibia nerve) ；感覺傳導速度測量的神經包括手部之正中神經(median nerve)與尺神經(ulnar nerve)，及腳部之腓腸神經(sural nerve)。MTHFR基因多形性是利用聚合酵素連鎖反應為基礎的限制片段長度多形性(PCR-RFLP)進行分析，檢測出本研究族群帶有突變T鹽基的頻率為0.27。研究結果發現，在控制性別、身高等危險因子後，停喝含砷地下水年數越高者，其正中神經及尺神經運動傳導速度越快。體內累積砷劑量越高者，其尺神經運動傳導、感覺傳導、脛神經運動傳導及腓腸神經感覺傳導速度越慢。營養素的攝取和神經傳導速度的相關性並不穩定。MTHFR基因多形性和神經傳導速度也沒有發現一致的相關。

The reduction of arsenic detoxification occurs mainly by methylation, which may compete with myelination and affect nerve conduction. In order to evaluate the association between nerve conduction velocity and arsenic exposure, and genetic polymorphisms of MTHFR, 130 junior high school students were selected. All of them were examed with the motor nerve conduction velocity on median nerve, ulnar nerve, peroneal nerve and tibia nerve, as well as the sensory nerve conduction velocities on median nerve, ulnar nerve and sural nerve. The concentration of arsenic in well water was obtained by matching the data with a cohort study performed in the same area in 1991. Other exposure data, for example, the years of drinking well water, the years of stop drinking well water, and the daily amount of drinking well water, were obtained from the questionnaires. Buccal mucosa were collected from each subject and genotyped for MTHFR by PCR-RFLP methods. The allele frequency of thymine in this study group was 0.27.
After adjusting the data with sex and height, motor nerve conduction velocities in median nerve and ulnar nerve in subjects with fewer years of stop drinking well water were significantly slower than the velocities in the others. Motor nerve conduction velocities in ulnar nerve and tibia nerve, as well as sensory nerve conduction velocity in ulnar nerve and sural nerve in subjects with higher amount of cumulative arsenic were significantly slower than the velocities in the others. The correlation between the intake of some vitamins and nerve conduction velocity is not obvious. Neither did the polymorphism of MTHFR affect the nerve conduction velocity.

致謝…………………………………………………………………………………….I
中文摘要……………………………………………………………………..………III
英文摘要…………………………………………………………………………..…IV
目錄…………………………………………………………………………………V
圖表目錄…………………………………………………………………….……..VII
第一章 前言…………………………………………...……………………………..1
第二章 文獻探討
第一節 砷的健康危害
（一） 砷的環境流佈…………………………………………………….5
（二） 砷在人體的代謝………………………………………………….6
（三） 砷的健康危害…………………………………………………….9
（四） 砷中毒對神經系統的影響……………………………………12
第二節 神經傳導速度
（一） 神經傳導………………………………………………………14
（二） 神經傳導速度檢查……………………………………………15
（三） 影響神經傳導的因子…………………………………………...17
第三節 MTHFR基因多形性
（一） MTHFR的作用………………………………………………….19
（二） MTHFR基因多形性…………………………………………….19
（三） MTHFR與疾病的關係…………………………………………20
第三章 材料與方法
第一節 研究地區及研究對象的選取
（一） 研究地區的選取………………………………………………...26
（二） 研究對象的選取………………………………………………26
第二節 研究對象基本資料和生物檢體的收集
（一） 基本資料的收集……………………………………………….27
（二） 生物檢體的收集………………………………………………...28
第三節 神經傳導速度的測量…………………………………………………28
第四節 實驗方法
（一） DNA萃取方法………………………………………………….30
（二） MTHFR基因型鑑定…………………………………………….31
第五節 資料處理與統計分析…………………………………………………36
第四章 結果
第一節 不同飲水砷濃度分組間相關因子的分佈情形
（一） 人口學特性、營養攝取情形在不同飲水砷濃度組間之分佈….41
（二） 砷暴露指標在不同飲水砷濃度組間之分佈…………………41
第二節 影響神經傳導速度各因子之單變項分析…………………………...42
第三節 砷暴露指標與神經傳導速度之線性迴歸分析……………………...43
第四節 砷暴露指標與神經傳導速度之多變項對數複迴歸分析…………...44
（一） 飲水累積砷劑量與神經傳導速度之對數複迴歸分析………45
（二） 停喝砷井水年數與神經傳導速度之對數複迴歸分析………...46
（三） 營養攝取情形與神經傳導速度之對數複迴歸分析…………...46
第五節 MTHFR基因多形性頻率分佈……………………………………….47
第六節 不同MTHFR基因型神經傳導速度之分佈…………………………48
第七節 MTHFR基因型與神經傳導速度之多變項對數複迴歸分析………48
第五章 討論
第一節 砷暴露與神經傳導速度之相關性探討
（一） 飲水砷濃度……………………………………………………..79
（二） 飲水累積砷劑量………………………………………………..79
（三） 停喝砷井水年數………………………………………………..80
第二節 MTHFR基因多形性與神經傳導速度之相關性探討……………81
第三節 營養素的攝取所扮演的角色……………………………………...82
第四節 各神經間的差異性………………………………………………...82
第六章 結論………………………………………………………….…………..84
第七章 研究限制…………………………………………………...……………85
參考文獻……………………………………………………………………………86
附錄………………………………………………………………..…………………96
圖表目錄
圖1-1、理論假說機制………………………………………………………………….4
圖2-1、無機砷在人體的代謝機制…………………………………………………….8
圖2-2、MTHFR在葉酸代謝過程中所扮演的角色…………………………………22
圖3-1、NCV檢測神經位置………………………………………………………….38
圖3-2、MTHFR基因多形性鑑定……………………………………………………39
圖3-3、MTHFR基因多形性二次確認鑑定…………………………………………40
圖4-1、飲水砷濃度與各運動傳導速度之線性迴歸分析…………………………...57
圖4-2、飲水砷濃度與各感覺傳導速度之線性迴歸分析…………………………...58
圖4-3、飲水累積砷劑量與各運動傳導速度之線性迴歸分析……...………………59
圖4-4、飲水累積砷劑量與各感覺傳導速度之線性迴歸分析……………………...60
圖4-5、停喝砷井水年數與各運動傳導速度之線性迴歸分析……………………...61
圖4-6、停喝砷井水年數與各運動傳導速度之線性迴歸分析……………………...62
表2-1、砷對週邊神經系統影響的相關文獻………………………………………...23
表2-2、MTHFR基因多形性之族群分佈……………………………………………24
表2-3、MTHFR基因多形性對神經系統影響的相關文獻…………………………25
表3-1、各神經傳導速度之測量距離…………………………….…………………29
表4-1、不同飲水砷濃度研究對象之人口學資料…………………………………...51
表4-2、不同飲水砷濃度研究對象之營養攝取情形……………………………….52
表4-3、不同飲水砷濃度研究對象之砷暴露指標分佈情形………………………...53
表4-4、研究對象人口學特性之神經傳導速度分佈情形…………………………...54
表4-5、不同營養攝取情形之研究對象其神經傳導速度分佈…………………….55
表4-6、研究對象之不同砷暴露指標神經傳導速度分佈情形……………………...56
表4-7、不同飲水砷濃度之研究對象其正中神經運動傳導速度與累積砷暴
露量、停喝井水年數及營養攝取情形分佈之對數複迴歸分析……...……63
表4-8、不同飲水砷濃度之研究對象其正中神經感覺傳導速度與累積砷暴
露量、停喝井水年數及營養攝取情形分佈之對數複迴歸分析………..…64
表4-9、不同飲水砷濃度之研究對象其尺神經運動傳導速度與累積砷暴露
量、停喝井水年數及營養攝取情形分佈之對數複迴歸……………….…65
表4-10、不同飲水砷濃度之研究對象其尺神經感覺傳導速度與累積砷暴露
量、停喝井水年數及營養攝取情形分佈之對數複迴歸分析…………….66
表4-11、不同飲水砷濃度之研究對象其腓神經運動傳導速度與累積砷暴露
量、停喝井水年數及營養攝取情形分佈之對數複迴歸分析…………….67
表4-12、不同飲水砷濃度之研究對象其脛神經運動傳導速度與累積砷暴露
量、停喝井水年數及營養攝取情形分佈之對數複迴歸分析…………….68
表4-13、不同飲水砷濃度之研究對象其腓腸神經感覺傳導速度與累積砷暴
露量、停喝井水年數及營養攝取情形分佈之對數複迴歸分析………….69
表4-14、研究對象之MTHFR基因多形性頻率分佈………………………………..70
表4-15、不同MTHFR基因型之研究對象其神經傳導速度分佈情形……………..71
表4-16、不同飲水累積砷劑量之研究對象其正中神經運動傳導速度與
MTHFR基因型分佈之對數複迴歸分析………………………………….72
表4-17、不同飲水累積砷劑量之研究對象其正中神經感覺傳導速度與
MTHFR基因型分佈之對數複迴歸分析………………………………….73
表4-18、不同飲水累積砷劑量之研究對象其尺神經運動傳導速度與MTHFR
基因型分佈之對數複迴歸分析…………………………………………...74
表4-19、不同飲水累積砷劑量之研究對象其尺神經感覺傳導速度與MTHFR
基因型分佈之對數複迴歸分析………………………………………….75
表4-20、不同飲水累積砷劑量之研究對象其腓神經運動傳導速度與MTHFR
基因型分佈之對數複迴歸分析…………………………………………...76
表4-21、不同飲水累積砷劑量之研究對象其脛神經運動傳導速度與MTHFR
基因型分佈之對數複迴歸分析………………………………………….77
表4-22、不同飲水累積砷劑量之研究對象其腓腸神經感覺傳導速度與
MTHFR基因型分佈之對數複迴歸分析………………………………….78

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