臺灣博碩士論文加值系統

高脂血症是因為血中三酸甘油脂或膽固醇異常的增加在體內血管脂肪堆積，導致血管徑狹窄的疾病。高脂血症除了飲食等環境因素外，近年來分子醫學的發展得知遺傳因子也佔了一大部份，這其中又以調節脂質代謝的apoE (apolipoprotein E，apoE)基因為主。所以欲研究台灣原住民的高脂血症與apoE多形性之間的相關。
本研究是以個案對照研究法(case-control study)與cross-selection 研究法來探討高脂血症與apoE基因多形性之間的相關。共收集355名分別來自三民鄉、春日鄉與牡丹鄉等地區中人口較集中的山地部落，主要以排灣族與布農族為研究對象。共355樣本數，經由測量T-C、TG、GOT、GPT及Cr等生化檢驗值來分類高脂血症。由血液中白血球來萃取DNA，利用聚合酶鏈作用(PCR)技術放大apoE基因，再以HhaI限制片段長度多型性(restriction fragment length polymorphism，RFLP)的方法，檢測各樣品apoE基因型的多型性。資料分析藉由SPSS 8.0與SAS 6.0版本軟體進行分析所收集的資料。高脂血症的定義為：高膽固醇血症(血中總膽固醇濃度≧200 mg/dl)；高三酸甘油酯血症(血中三酸甘油酯濃度≧200 mg/dl)。
研究結果顯示355名個案中，初步分析時將組別分為正常血脂與否，得到高脂血症組的T-C、GOT、TG均有意義高於正常血脂組。得到GOT、T-C與TG在不同高脂血症組間有顯著性差異。此外有痛風及有飲酒的人在高脂血症組與正常血脂組之間有顯著性差異。將高脂血症組再分高膽固醇組(總膽固醇≧200 mg/dl)13人、高三酸甘油脂組(TG≧200mg/dl)131人、合併組(總膽固醇≧200mg/dl且TG≧200mg/dl)30人及正常血脂當對照組179人，分析結果與前者一致。高膽固醇且帶有ε4基因型的人是正常血脂且無ε4基因型者的2.67倍(OR=2.674，95%CI=1.033-6.922)。有飲酒且無E4基因型是正常血脂且無E4基因型者的2.773倍(OR=2.773，95%CI=1.408 -5.459)。此外吸煙、痛風的有無都是造成較高的危險對比值(OR)，但是沒有達顯著性差異。
比較apoE常見的ε2、ε3與ε4在高脂血症組個案中的頻率分別為3% (ε2)、87. 2%(ε3)、9.8%(ε4)分佈，本研究的結果與其他研究結果有差異。可知種族對apoE頻率有影響。正常血脂組apoE各對偶基因出現的頻率分別為1.4%(ε2)、89.8%(ε3)、8.8%(ε4)。帶ε2對偶基因頻率在高脂血症組是正常血脂組的2倍，但未達明顯的差異(p=0.653)。所以由本研究結果可知高脂血症是環境因子與遺傳因子交互作用下的多因子疾病，單是遺傳因子(apoE gene)並不是那麼容易引起高脂血症。

Hyperlipoproteinemia is serum cholesterol and triglyceride concentrations increase . hyperlipoproteinemia’s risk factors involve the environment that diet ,fatness, other diseases and smoking and genomic that apoE, apoC-Ⅲ .This study investigates the correlation of apoE polymorphisms and hyperlipoproteinemia in Chinese aborigine subjects. We use the case-control study and cross selection study in this research.
DNA from 355 individuals was used for polymerase chain reaction(PCR) amplification of the three apoE alleles. The amplified products were analyzed by HhaI restriction fragment length polymorphism(RFLP) and sequence analysis. Indentical genotypes were obtained by both methods in all individuals analyzed. The allele frequency between hyperlipoproteinemia and normal lipoprotein were 3% for epsilon 2, 87.2% for epsilon 3 and 9.8% for epsilon 4 in hyperlipoproteinemia and 1.4% for epsilon 2, 89.8% for epsilon3 and 8.8% for epsilon 4 in normal lipoprotein .
Result shows in table 4-5, hyperlipoproteinemia were T-C, GOT and TG significance higher than normal lipoprotein .Table 6 shows hypercholesterolemia, mixed hyperlipidemia and hypertriglyceridemia. The result is the same table 4 and 5.The prevalence of the six apolipoproteine phenotypes in the hyperlipoproteinemia individuals and in the control group.The results demonstrate that neither the epsilon 2 nor epsilon 4 alleles affect cholesterol values in Taiwan aborigines subjects.

誌謝 Ⅰ
目錄 Ⅱ-Ⅲ
中文摘要 Ⅳ-Ⅴ
英文摘要 Ⅵ-Ⅶ
第一章 緒論　　　
第一節　研究背景與動機 1-2
第二節　研究目的 3
第三節 研究假設 3
第二章　 文獻探討　　　　
第一節　脂蛋白特性 4-6　
第二節 高脂血症(hyperlipoproteinemia) 7-9 第三節　apolipoprotein E(apoE)基因 10-12 第四節 高脂血症與apoE 基因相關性 13-15
第三章　 研究材料、方法與步驟　　　
第一節 研究流程 16
第二節 研究設計 17
第三節 研究族群 19
第四節 資料收集 20
第五節 血樣生化分析apoE表現型態 20
第六節 實驗室分析apoE基因型態 21-25
第七節 定義變項 26
第八節 資料統計分析　　 27
第四章　結果　
第一節　研究對象基本資料 28-29　
第二節　高脂血症相關因子探討 29-30　
第三節 apoE基因型分布 31
第五章　討論與建議　　 32-34
第六章　參考文獻 35-50
附圖 51-55
附表 56-62

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