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研究生:沈長融
研究生(外文):Shen, Chang-Jung
論文名稱:晝夜節律相關基因多形性、日韻律型態與代謝症候群:相關性與交互作用分析
論文名稱(外文):Alterations in circadian rhythms and metabolic syndrome: effects of chronotype and polymorphisms in chronotype-associated and circadian-related genes
指導教授:周雨青周雨青引用關係
指導教授(外文):Chou, Yu-Ching
口試委員:孫建安白其卉周雨青
口試委員(外文):Sun, Chien-AnBai, Chyi-HueyChou, Yu-Ching
口試日期:2018-05-11
學位類別:碩士
校院名稱:國防醫學院
系所名稱:公共衛生學研究所
學門:醫藥衛生學門
學類:公共衛生學類
論文種類:學術論文
論文出版年:2018
畢業學年度:106
語文別:中文
論文頁數:216
中文關鍵詞:日韻律型態日韻律型態相關基因晝夜節律相關基因基因多型性代謝症候群
外文關鍵詞:ChronotypeChronotype-related genecircadian-related genegene polymorphismmetabolism syndrome
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代謝症候群是代謝異常聚集的疾病,其發生率在現代化國家持續上升,近年研究結果顯示晝夜節律失衡與睡眠障礙是代謝症候群重要的致病因子。日韻律型態為個體獨特的晝夜節律,與人體晝夜節律基因相關聯,如兩者交互作用下,勢必對人體生理機制造成影響。本研究為以社區為基礎之病例對照研究,病例組為273名代謝症候群患者,對照組為730名配對之健檢民眾;以問卷收集基本人口學變項與日韻律型態的資料,並進行體位測量與採集10毫升靜脈血作為實驗分析檢體,利用OpenArray 系統進行候選基因定型。以邏輯斯迴歸分析基因多形性與代謝症候群及其組成因子關聯性,利用日韻律型態分層,探討其修飾作用。本研究結果顯示,有無考慮日韻律型態修飾晝夜節律基因多型性與代謝症候群及其組成因子的關聯性下,發現各基因位點影響代謝症候群方向與文獻存在差異,我們不僅要考量基因型別的差異存在健康風險,仍可利用更多晝夜節律相關環境因素作考量,如睡眠品質問卷或納入體內生物標記(如褪黑激素) 與基因多型性一同探討,並討論對於代謝症候群及其組成因子之關聯性是否存在修飾作用,且進一步探討其途徑機轉。

關鍵字:日韻律型態、晝夜節律基因、基因多型性、代謝症候群
Recent evidence has emerged to suggest that alterations in circadian systems and sleep play important roles in the pathogenesis of the MetS. Chronotype is a trait determining individual circadian preference in behavioral and biological rhythm relative to external light-dark cycle. Previous studies have uncovered that several common polymorphisms in the circadian-related genes are involved in the development of type 2 diabetes and cardiovascular disease. However, very limited research has been completed on the associations of genetic polymorphism in chronotype-associated and circadian-related genetic loci with the MetS. The aims of the proposed study is to investigate the relationships of chronotype and polymorphisms in the circadian-related genes with the risk of MetS. A total of 273 cases with MetS and 730 matched control subjects were recruited from the Show-Chwan Memorial Hospital in the Changhua area. All participants responded to an interviewer-administerd questionnaire to collect data on sociodemographic factors, lifestyle characteristics, and personal history of disease, and underwent a comprehensive physical examination. In addition, a blood sample was drawn from each participant after an overweight fast. In this study, chronotype will be assessed by the Horne-Ostberg Morningness-Eveningness Questionnaire. Single nucleotide polymorphisms (SNPs) in the chronotype-associated and circadian-related genes will be genotyped by TaqMan OpenArray Genotyping Plates. Genotyping will validate sequences of SNPs 10% of blinded samples in duplicate to assure the concordance. Multivariable conditional logistic regression analyses will be conducted to test study hypotheses. After stratifying patterns of chronotype, our results provide the surprising insight. The risk allele may influence dynamics of melatonin secretion and activity of fibroblast cells, generating a novel hypothesis that the interaction between chronotype and risk allele may revise the Mets risk. The mechanism of these findings still need to be research.

Key words:chrnotype, chrnotype-related gene, circadian-related gene, gene polymorphism, metabolism syndrome
第一章、緒論 2
第一節、研究背景與重要性 2
第二節、研究目的 7
第二章、文獻探討 8
第一節、代謝症候群 8
第二節、生理晝夜節律 14
第三節、日韻律型態與代謝症候群因子探討 17
第四節、晝夜節律及日韻律型態相關基因與代謝症候群因子探討 20
第三章、研究方法 36
第一節、研究設計與研究對象 36
第二節、資料收集 37
第三節、統計分析 51
第四章、研究結果 58
第一節、研究對象基本特性、生活型態分佈情形 58
第二節、依日韻律型態比較研究對象基本特性、生活型態分佈情形 61
第三節、研究對象基因多形性之分佈情形 69
第四節、基因多形性與代謝症候群之相關性分析 74
第五節、日韻律型態對基因與代謝症候群關聯之修飾 79
第六節、基因多形性與高血壓之相關性分析 86
第七節、日韻律型態對基因與高血壓關聯的修飾作用 90
第八節、基因多形性與高血糖之相關性分析 96
第九節、日韻律型態對基因與高血糖關聯之修飾 100
第十節、基因多形性與高三酸甘油脂之相關性分析 105
第十一節、日韻律型態對基因與高三酸甘油脂關聯之修飾 109
第十二節、基因多形性與低高密度膽固醇之相關性分析 114
第十三節、日韻律型態對基因與低高密度膽固醇關聯之修飾 118
第十四節、基因多形性與肥胖(BMI≥27)之相關性分析 124
第十五節、日韻律型態對基因多形性與肥胖關聯之修飾 128
第十六節、基因多形性與腹部肥胖之相關性分析 134
第十七節、日韻律型態對晝基因與腹部肥胖關聯之修飾 138
第十八節、單套體多形性與分佈情形 144
第十九節、單套體多形性與代謝症候群及其相關因子之相關性分析 146
第二十節、日韻律型態對單套體多形性與代謝症候群關聯之修飾 155
第五章、討論 172
第一節、晝夜節律候選基因多形性與代謝症候群之關係 172
第二節、基因間或與環境因子對於代謝症候群之關聯性的修飾作用 189
第六章、結論 201
參考文獻 203

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