臺灣博碩士論文加值系統

背景
巴金森氏病是一種神經退行性疾病，其病因複雜且難以捉摸，涉及遺傳、行為和環境因素之間的複雜互動。近年來，尤其是DNA甲基化的表觀遺傳修飾已被認為是透過生活方式干預或環境因素對巴金森症發病起著重要作用。本論文探討了兩個主要方面：運動和性別對GPNMB cg17274742甲基化水平的影響，以及GPNMB rs199347變異與酒精使用對GPNMB蛋白甲基化的交互作用。
方法
研究數據來自台灣生物庫2008年至2016年期間收集的數千名參與者。針對運動和性別的分析，包括了1,442名數據完整的參與者。針對酒精使用和GPNMB rs199347變異的評估，分析了1,357名參與者。使用Illumina Infinium MethylationEPIC測量GPNMB cg17274742 CpG位點的甲基化水平。採用多元線性回歸模型進行分析，調整了年齡、BMI、吸菸、飲酒、咖啡消費、血清尿酸水平和高血壓等因素。
結果
本研究分為兩個部分：
1.運動和性別：
身體活動顯著降低了男性的GPNMB cg17274742甲基化水平（β = -0.00242；p = 0.0026），但對女性無顯著影響（β = -0.00002362；p = 0.9785）。
參與運動的男性的甲基化水平顯著低於不運動的男性和女性（β = -0.00357；p = 0.0079）。
性別和運動對GPNMB cg17274742甲基化水平的交互作用顯著（p = 0.0078）。
2.酒精使用和GPNMB rs199347變異：
GPNMB rs199347變異與酒精使用之間存在顯著的交互作用（p = 0.0102）。
攜帶rs199347 GG基因型且使用酒精的個體與不飲酒的AA基因型個體相比，顯示出顯著較低的cg17274742甲基化水平（p = 0.0187）。
結論
本研究強調了運動和性別對GPNMB cg17274742甲基化的表觀遺傳調控，發現男性運動者出現低甲基化。此外，研究顯示酒精消費在攜帶rs199347 GG基因型的個體中對GPNMB甲基化水平有顯著影響。這些發現表明，生活方式因素如運動和酒精使用，結合遺傳易感性，可能通過表觀遺傳機制影響巴金森氏症風險。需要進一步研究以了解其背後的機制及其對巴金森氏症預防策略的潛在影響。

Purpose
Parkinson's disease (PD) is a multifaceted neurodegenerative disorder with an elusive etiology that involves a complex interplay between genetic, behavioral, and environmental factors. Epigenetic modifications, particularly DNA methylation, have emerged as significant contributors to PD onset through lifestyle interventions or environmental factors. This thesis explores two primary aspects: the influence of exercise and gender on the methylation levels of GPNMB cg17274742, and the interaction between the GPNMB rs199347 variant and alcohol consumption on methylation upstream of GPNMB.
Material and Methods
Data were retrieved from thousands of participants in the Taiwan Biobank, collected between 2008 and 2016. For the analysis of exercise and gender, 1,442 participants with complete data were included. For the evaluation of alcohol consumption and the GPNMB rs199347 variant, 1,357 participants were analyzed. Methylation levels at the GPNMB cg17274742 CpG site were measured using Illumina Infinium MethylationEPIC beads. Multiple linear regression models were employed to assess associations, adjusting for age, BMI, smoking, drinking, coffee consumption, serum uric acid levels, and hypertension.
Results
The thesis is divided into two sections.
1. Exercise and Gender:
Physical activity significantly decreased GPNMB cg17274742 methylation levels in males (β = -0.00242; p = 0.0026), but not in females (β = -0.00002362; p = 0.9785).
Men who engaged in exercise showed lower methylation levels compared to both non-exercising men and women (β = -0.00357; p = 0.0079).
There was a significant interaction between gender and exercise on GPNMB cg17274742 methylation levels (p = 0.0078).
2. Alcohol consumption and GPNMB rs199347 Variant:
A notable interaction was found between the GPNMB rs199347 variant and alcohol consumption (p = 0.0102).
Individuals with the rs199347 GG genotype who consumed alcohol exhibited significantly lower cg17274742 methylation levels compared to non-drinkers, with the AA genotype (p = 0.0187).
Conclusion
This study highlights the epigenetic modulation of GPNMB cg17274742 methylation by exercise and gender, with hypomethylation observed in exercising males. Additionally, it reveals the significant impact of alcohol consumption in individuals with the rs199347 GG genotype on GPNMB methylation levels. These findings suggest that lifestyle factors, such as exercise and alcohol consumption, in conjunction with genetic predispositions, may influence PD risk through epigenetic mechanisms. Further research is essential to understand the underlying pathways and their potential for informing PD prevention strategies.

謝誌 I
中文摘要 II
結論 III
Abstract IV
Conclusion V
目次 VI
表次 VII
Chapter I Introduction 1
Chapter II Literature Reviews 4
Chapter III Methods 6
Chapter IV Results 9
Chapter V Discussion 20
Chapter VI Conclusion 23
Chapter VII References 24

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