臺灣博碩士論文加值系統

中文摘要
研究背景與目的：近幾年來，不管是一般大眾或者是精神分裂症（schizophrenia）患者，其代謝異常症狀已引起多方關注。代謝異常症狀是一群會引發心血管疾病的因子，包括肥胖、血脂異常、高血壓、高血糖等。異常結果，常會一併發生，人們把這些現象亦稱為代謝症候群（metabolic syndrome；Mets）。目前已知，代謝症候群會增加死亡率、心血管疾病及中風罹患率，且其致病機轉仍不清楚，而其盛行率一區域差異甚大暗示著基因可能是一個調控因子。載脂蛋白Apo（apolipoprotein）E是低密度脂蛋白VLDL、chylomicron remnants 及 高密度脂蛋白HDL的部分組成物。ApoE可以和apoE receptor及LDL receptor鍵結，在脂質代謝中扮演一個重要角色。一般認為過度飲食與久坐的生活模式與代謝症候群有所關聯，血清素（serotonin, 5-HT）系統和許多行為有關，其中一項就是進食；許多研究發現，抗精神病藥物引起之體重增加與5-HT2C receptor基因多型性有關，近年來也有文獻指出5-HT2C receptor 基因多型性指出與精神分裂症病人之代謝症候群有關。過氧化小體增生劑活化接受體Peroxisome proliferator-activated receptor , gamma (PPARγ)是細胞核內類固醇受體之一，PPARγ被認為與脂質代謝有關。綜合上述而知，ApoE、5-HT2C ､PPARγ可能與代謝症候群有些關連性存在。因此本研究主要探討精神分裂症代謝症候群與ApoE、5-HT2C ､PPARγ之基因多型性是否有關連性存在。
研究方法：本研究之研究對象為台灣某醫院之精神分裂症患者，收集300位經精神科專科醫師依據DSM-IV診斷為精神分裂症或情感性精神分裂症患者之年度健檢資料共350位，再依據2005年「美國國家膽固醇教育計劃成人治療指引第三版之修訂版（updated NCEP-ATP III）」的代謝症候群診斷標準（亞洲）由醫師作代謝症候群與否之診斷，於99年收案時共計得202位病患(其中61位為Mets及141位為non-Mets) 分析PPARγ Pro12Ala基因；100年收案2組，第一組共計得224位病患 (其中68位為Mets及156位為non-Mets) 分析ApoE基因，第二組共計得226位病患 (其中69位為Mets及157位為non-Mets) 分析HTR2C基因。利用PCR-RFLP的技術方法分析ApoE、5-HT2C ､PPARγ基因型分佈，再利用統計軟體進行統計分析。
研究結果：1.精神分裂症患者之PPARγ Pro12Ala及HTR2C Cys23Ser基因多型性不論是P allele或A allele與C allele或S allele的出現，皆不會導致代謝症候群的風險增加；2.精神分裂症患者之ApoE基因多型性在E3/E4型較E3基因型發生代謝症候群的風險增加2.431倍；3.ApoE基因多型性在E4單套體型較E3單套體型發生代謝症候群的風險增加 2.092倍，皆達統計學上顯著差異的標準(P<0.05)。

英文摘要
Background and Purpose: The schizophrenic patients have higher prevalence of metabolic syndrome than general population. Some association between HTR2C and metabolic syndrome was found. Apo E and Peroxisome proliferator-activated receptor are associated with the lipid metabolism. The aim of this study was to determine the association between gene polymorphisms and metabolic syndrome.
Methods: After obtaining the permission of IRB, we plan to enroll 300 schizophrenic or schizoaffective patients in Jianan Mental Hospital. The diagnosis of metabolic syndrome is done by updated version of NCEP-ATP III for Asia. The polymorphism is checked by PCR-RFLP. All these 300 patients receive genetic polymorphism analysis of the ApoE polymorphism、HTR2C polymorphism and PPARγ polymorphism.
Results: There is no association between PPARG Pro12Ala and HTR2C Cys23Ser with metabolic syndrome in enrolled 202 and 226 patients.ApoE polymorphism in our population 226 patients (69.12% for E3/E3 , 25% for E3/E4 , 2.94% for E2/E3 , 2.94% for E2/E2) were in agreement with those reported for Romania and other Caucosion populations. The distribution of ApoE alleles indicated a higher frequency of E4 (P<0.05) in groups E2 and E3.
Conclusion: Correlations of apoE genotypes with these markers indicate that the E4 allele is an independent risk factor for metabolic syndrome.
Keyword：Schizophrenia、Metabolic Syndrome、Gene Polymorphism

目錄
審定書
授權書
目錄 Ⅰ
圖目錄 IV
表目錄 V
謝誌 VI
中文摘要 VIII
Abstract XI
第一章、文獻回顧 1
第一節、精神分裂症..........................................................................1
壹、精神分裂症之定義..............................................................1
貳、精神分裂症之演變..............................................................1
參、精神分裂症之流行病學......................................................4
肆、精神分裂症之常見症狀......................................................4
伍、精神分裂症之發病病程......................................................5
陸、精神分裂症之分類..............................................................6
柒、精神分裂症之病因..............................................................7
第二節、代謝症候群..........................................................................9
壹、代謝症候群之演變................................................................9
貳、代謝症候群之臨床診斷標準..............................................10
1. 國外代謝症候群之臨床診斷標準...............................10
2. 國內代謝症候群之臨床診斷標準...............................13
參、代謝症候群之核心異常......................................................14
1. 代謝症候群與肥胖.......................................................14
2. 代謝症候群與胰島素阻抗...........................................15
3. 代謝症候群與基因及其他危險因子...........................17
4. 罹患代謝症候群之高風險因素（流行病學）.............19
第三節、精神分裂症與代謝症候群之相關性探討..........................21
第四節、 ApoE、5-HT2C及PPARγ基因與代謝症候群...............22
1. Apoe基因與代謝症候群...............................................22
2. 5-HT2C基因與代謝症候群..........................................24
3. PPARγ基因與代謝症候群...........................................25
第二章、研究目的.....................................................................................29
第三章、研究方法......................................................................................30
第一節、研究對象.............................................................................30
第二節、基因檢測..............................................................................30
第三節、研究流程及方法.................................................................32
第四節、統計分析..............................................................................43
第四章、研究結果 44
第五章、討論 48
第六章、結論 52
第七章、參考文獻.................................................................................... 53
第八章、圖與表....................................................................................... 71
圖目錄
圖一、ApoE PCR結果之電泳圖......................................................... 71
圖二、5-HT2C Cys23Ser PCR結果之電泳圖......................................72
圖三、PPARγPro12Ala PCR結果之電泳圖....................................... 73
圖四、ApoE RFLP結果之電泳圖....................................................... 74
圖五、5-HT2C Cys23Ser RFLP結果之電泳圖....................................75
圖六、PPARγ Pro12Ala RFLP結果之電泳圖.................................... 76








表目錄
表一、研究人口之參數........................................................................ 77
表二、精神分裂症患者代謝症候群與基因多型性之分析................ 78
表三、精神分裂症患者代謝症候群與基因單套體之分析.................79

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