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完整後設資料紀錄
DC 欄位 | 值 | 語言 |
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dc.contributor.advisor | 潘文涵 | |
dc.contributor.author | Hsin-Hung Chen | en |
dc.contributor.author | 陳信宏 | zh_TW |
dc.date.accessioned | 2021-06-12T18:28:01Z | - |
dc.date.available | 2008-08-28 | |
dc.date.copyright | 2007-08-28 | |
dc.date.issued | 2007 | |
dc.date.submitted | 2007-08-08 | |
dc.identifier.uri | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/27921 | - |
dc.description.abstract | 中文摘要
過去30年來,全世界肥胖的盛行率有急速上昇的趨勢。肥胖不僅是許多慢性疾病的危險因子,也會影響到肥胖患者的生活品質及人際關係。而有效的減重可以改善肥胖患者血糖及血脂異常的情況,並降低肥胖患者各種疾病的風險。許多文獻指出,不同的種族會受到不同肥胖基因的影響,但至目前為止,很少有針對台灣的漢族群做系統性肥胖基因篩選的研究。加上近年來台灣肥胖的盛行率也有逐年升高的趨勢,所以找出對於漢族群貢獻較大的致肥胖基因,並應用於肥胖的防治上,將是當務之急。本研究利用病例對照的相關性研究法,尋找出對於漢族群貢獻較大的致病態型肥胖基因。另外,我們也將探討這些致病態型肥胖基因是否會影響減重手術的成效,以便未來應用於手術前的篩選。同時為符合成本效益,我們原本打算以gDNA pooling 的方式進行相關性研究,但卻發現以κ校正法所估計的對偶基因頻率在某些情況下與實際值有系統性的誤差存在。因此我們試圖發展一個較佳的 DNA pooling 校正法,期望未來可以將之應用於大型的基因相關性試驗。 研究一 搜尋台灣病態型肥胖重要易感受基因 本研究是針對居住於台灣的漢族群做系統性的肥胖基因篩選,希望能找出對於漢族群貢獻較大的致病態型肥胖基因。我們總共收集304位BMI | zh_TW |
dc.description.abstract | Abstract
The prevalence of obesity has been growing rapidly worldwide in the last 30 years. Obesity is not only a major public health concern but also considered as an important risk factor of various chronic diseases. Conversely, weight loss for obese patients can make a substantial contribution to reducing hyperlipidemia, improving glycemic control, treating hypertension and decreasing the risk of dying from cancer. Evidences from many litetures have obviously shown that obesity and weight loss for obese patients are strongly influenced by genes and environments, but previous studies showed heterogeneous findings on potential obesity loci, using large variety of obesity phenotypes across multiple populations. Yet there are relatively few systematic studies in Han Chinese to screen for obesity and weight loss prognostic genes. Hence our study is the first of its kinds in Han Chinese to search for major obesity genes and weight loss prognostic genes after bariatric surgeries, using morbid obesity (BMI | en |
dc.description.provenance | Made available in DSpace on 2021-06-12T18:28:01Z (GMT). No. of bitstreams: 1 ntu-96-D89623703-1.pdf: 2128398 bytes, checksum: d395c1d64d9ef46fc0ff6f10d134a74d (MD5) Previous issue date: 2007 | en |
dc.description.tableofcontents | 目錄
摘要...........................................................................................................................................1 ABSTRACT..............................................................................................................................5 第一章 前言..........................................................................................................................11 第二章 文獻回顧..................................................................................................................14 第一節 肥胖外表型.......................................................................................................................................14 第二節 肥胖的成因.......................................................................................................................................15 A. 生理調控的異常..................................................................................................................................15 B. 基因的因素..........................................................................................................................................18 C. 環境的因素..........................................................................................................................................19 D. 基因與環境的交互作用.......................................................................................................................19 第三節 遺傳流行病學 -- 相關性(ASSOCIATION STUDY)研究法..............................................................21 A. 以家庭成員為主的相關性研究法(Family-based association study) .............................................21 B. 病例對照(Case-control association study)研究法..........................................................................22 第四節DNA POOLING 的研究.......................................................................................................................24 第五節 人類肥胖基因的研究........................................................................................................................29 A. 肥胖外表型的遺傳率(Heritability)研究.........................................................................................29 B. 與人類肥胖具影顯著相關性的候選基因............................................................................................32 I. 影響脂質代謝相關的基因...............................................................................................................................57 II. 脂肪細胞激素(Adipokines/Adipocytokines) 相對應的基因...........................................................................64 III. 影響食慾相關的基因......................................................................................................................................67 IV. 影響神經訊息的接收 / 能量代謝改變的相關基因......................................................................................68 C. 與環境因素交互作用改變肥胖外表型的基因...................................................................................72 I. 與減重手術(Bariatric surgery)交互作用改變肥胖外表型的基因...............................................................72 II. 與藥物交互作用改變肥胖外表型的基因........................................................................................................73 III. 與運動交互作用改變肥胖外表型的基因.......................................................................................................74 IV. 與飲食交互作用改變肥胖外表型的基因.......................................................................................................74 第三章 研究目的..................................................................................................................79 第四章 材料與方法..............................................................................................................81 第一節 搜尋台灣漢族群病態型肥胖基因及減重手術預後基因................................................................81 A. 研究設計............................................................................................................................................81 B. 肥胖外表型的選擇.............................................................................................................................81 C. 受試者來源..........................................................................................................................................82 I. 病例組..........................................................................................................................................................82 2 II. 對照組..........................................................................................................................................................82 D. 候選基因資料的收集...........................................................................................................................83 E. gDNA 的抽取與基因型鑑定..............................................................................................................84 I. gDNA 的抽取......................................................................................................................................................84 II. 基因型鑑定.......................................................................................................................................................85 F. mRNA 的表現 (Quantitative PCR)....................................................................................................86 G. 統計分析..............................................................................................................................................88 I. 第一階段相關性研究的分析(The first stage) ...............................................................................................88 II. 第二階段相關性研究的分析(The second stage) .........................................................................................88 III. 減重手術預後基因的分析...............................................................................................................................89 IV. 基因mRNA 表現的統計分析..........................................................................................................................89 第二節 DNA POOLING 試驗...........................................................................................................................90 A. 研究設計..............................................................................................................................................90 B. gDNA 檢體的定量..............................................................................................................................90 C. SNPs 的選擇......................................................................................................................................91 D. gDNA 集合檢體及標準檢體的製備..................................................................................................91 I. gDNA 集合檢體的製備...............................................................................................................................91 II. 標準檢體的製備..........................................................................................................................................93 E. SNaPshot TM反應................................................................................................................................94 F. gDNA 集合檢體內對偶基因頻率的估算...........................................................................................95 第五章 研究結果....................................................................................................................96 第一節 搜尋台灣病態型肥胖重要易感受基因............................................................................................97 第二節 搜尋貢獻較大的減重手術成效之預後基因..................................................................................124 第三節 使用標準化曲線估算GDNA 集合檢體的對偶基因頻率................................................................145 第六章 總結..........................................................................................................................169 參考文獻................................................................................................................................171 附錄一 病態型肥胖之病例對照研究法搜尋台灣人較重要的致肥胖與代謝症候群基因 計畫同意書............................................................................................................................210 附錄二 敏盛綜合醫院人體試驗委員會通過許可書........................................................213 附錄三 財團法人恩主公醫院人體試驗委員會通過許可書............................................214 附錄四 肥胖及代謝症候群基因搜尋計畫之受試個案問卷記錄......................................215 附錄五 SEQUENOM MASSARRAY® 的原理...............................................................227 附錄六 SEQUENOM-MALDI-TOF 平台分析GNB3-A657T 所出現的不正常圖譜..228 | |
dc.language.iso | zh-TW | |
dc.title | 搜尋台灣病態型肥胖重要易感受基因及減重手術成效之預後基因暨發展新的DNA集合檢體比較法以應用於相關性研究分析 | zh_TW |
dc.title | Searching for Influential Morbid Obese Genes and Prognostic Genes for Bariatric Surgeries in Taiwan Han Chinese and Developing Novel DNA Pooling Methods for Association Study | en |
dc.type | Thesis | |
dc.date.schoolyear | 95-2 | |
dc.description.degree | 博士 | |
dc.contributor.oralexamcommittee | 李威傑,張新儀,周玉山,范盛娟 | |
dc.subject.keyword | 肥胖基因,病態型肥胖,減重手術,預後基因,gDNA 集合檢體, | zh_TW |
dc.subject.keyword | morbid obesity,Chinese Han,obese genes,bariatric surgery,gene,gDNA pooling,polynomial standard curves, | en |
dc.relation.page | 228 | |
dc.rights.note | 有償授權 | |
dc.date.accepted | 2007-08-08 | |
dc.contributor.author-college | 生命科學院 | zh_TW |
dc.contributor.author-dept | 微生物與生化學研究所 | zh_TW |
顯示於系所單位: | 微生物學科所 |
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