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研究生: 戴文
Dai, Wen
論文名稱: 單胺氧化酶B單一核苷酸多型性對巴金森氏病患者執行功能之影響
The Effect of Monoamine Oxidase B (MAOB) rs1799836 G Allele Polymorphism on The Executive Functions in Parkinson’s Disease Patients
指導教授: 余睿羚
Yu, Rwei-Ling
學位類別: 碩士
Master
系所名稱: 醫學院 - 行為醫學研究所
Institute of Behavioral Medicine
論文出版年: 2020
畢業學年度: 108
語文別: 英文
論文頁數: 37
中文關鍵詞: 巴金森氏病單胺氧化酶B執行功能多巴胺多巴胺過量假說
外文關鍵詞: Parkinson’s Disease, monoamine oxidase B (MAOB), executive function, dopamine, dopamine overdose hypothesis
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  • 研究目的:執行功能為巴金森氏病患者重要的認知功能缺損範疇。然而,多巴胺代謝所需的單胺氧化酶B對巴金森氏病患者的執行功能影響尚未釐清。本研究主要探討單胺氧化酶B內含子13之單一核苷酸多型性對於巴金森氏病患者的執行功能影響。
    方法:本研究共納入64位巴金森氏病患者,每位個案個別施測世界動作障礙學會巴金森病綜合評量表 (MDS–UPDRS)、簡式心智量表(MMSE)、以及其他執行功能相關神經認知功能測驗。施測完成後採集10毫升靜脈血以進行單一核苷酸多型性基因型檢測。神經認知功能測驗結果以單因子變異數分析、克-瓦單因子變異數分析或排序共變數分析進行檢定。
    結果:研究結果顯示帶有G對偶基因的男性巴金森氏病個案相較於帶有A對偶基因的個案,在記憶廣度的順序與逆序背誦廣度差值表現較佳 (H(1, N=42) = 5.421, p = .020, η2 = .132),然而在語意流暢度測驗15至30秒間的字詞數量表現較差 (H(1, N=42) = 5.623, p = .018, η2 = .137)。在女性中,雖然在記憶廣度的順序背誦中有顯著差異 (H(2, N=22) = 7.059, p = .029, η2 = .336),但事後比較三組不同基因型的女性,彼此間並沒有任何一個組合達到顯著差異。若將男性與女性資料合併分析,在控制性別與教育程度的情形下,並沒有觀察到在神經認知功能上有顯著差異。
    結論:綜上,本研究結果顯示單胺氧化酶B內含子13的G對偶基因有利於男性巴金森氏病個案的工作記憶,但與較低的認知彈性有關。

    Objective: Executive dysfunction is an important cognitive disturbance in patients with Parkinson’s disease (PD). However, the role of monoamine oxidase B (MAOB), which is an important enzyme in dopamine metabolism, in the executive function of patients with PD remains debated. The objective of this study is to investigate the effect of MAOB single nucleotide polymorphism (SNP) in intron 13 (rs1799836) on the executive function in PD patients.
    Methods: Sixty-four PD patients were enrolled in this study. Participants were individually administered part III of the Movement Disorder Society-sponsored revision of the Unified Parkinson's Disease Rating Scale (MDS–UPDRS), Mini-Mental State Examination (MMSE), and neuropsychological tests. Ten-milliliter venous blood was then collected for genotyping. The results of neuropsychological tests were examined by one-way ANOVA, Kruskal-Wallis test, or Quade’s rank analysis of covariance.
    Results: Male PD patients with G allele in MAOB SNP in intron 13 showed lower performance on the number of word counts in Verbal Fluency test during 15 to 30 seconds (H(1, N=42) = 5.623, p = .018, η2 = .137) but higher on the span difference in Digit Span Subtest of Wechsler Adult Intelligence Scale-Third Edition (DS) (H(1, N=42) = 5.421, p = .020, η2 = .132). On the other hand, even though female PD patients showed a significant difference in the forward span in DS (H(2, N=22) = 7.059, p = .029, η2 = .336), there is no significant difference in the post-hoc analysis. After pooling all participants, analysis done by Quade’s rank analysis of covariance with covariates of sex and education showed no significant difference in all neuropsychological measurements.
    Conclusion: In summary, G allele in MAOB SNP in intron 13 benefits the working memory function but decreases the cognitive flexibility in male PD patients.

    Chapter 1 Introduction 1 Chapter 2 Literature Review 2 Section 1 Parkinson’s Disease 2 Section 2 Cognitive Dysfunction and Dopamine Metabolism in PD Patients 6 Section 3 Single Nucleotide Polymorphism of Monoamine Oxidase B (MAOB) 10 Chapter 3 Aims and Hypothesis 11 Chapter 4 Methods 12 Section 1 Participants 12 Section 2 Research Procedure 12 Section 3 DNA Extraction and Genotyping 13 Section 4 Cognitive Function Assessments 13 Section 5 Statistical Analysis 16 Chapter 5 Results 18 Section 1 Analysis of Genetic Polymorphism 18 Section 2 Demographic Characteristic 18 Section 3 The Effect of MAOB Polymorphism on Neuropsychological Functions in PD Patients 21 Chapter 6 Discussion 27 Section 1 Summary 27 Section 2 The Neuropsychological Findings 27 Section 3 The Sex-dependent Effects of MAOB G-A SNP on The Executive Function of PD Patients 29 Section 4 Research Limitations 30 Section 5 Conclusion 31 References 32

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