臺灣博碩士論文加值系統

背景
唐氏症(Down syndrome; DS)為目前國內最常造成智能障礙的染色體疾病之一，雖然目前國內的醫療技術已將產前篩檢唐氏症的機率提高，但還是會有一些孕婦可能因為未做唐氏症篩檢而生下唐氏症的小孩。這些家庭除了必須面對唐氏症患者成長過程中的教養問題，到了唐氏症患者更年期時，就可能必須考慮到後續更加困難的照護問題，例如退化性疾病像是失智症(Dementia)的發生。這些後續出現的問題會造成這些唐氏症患者在精神上及生活上的照顧更加困難，加重照顧者的負擔。然而，造成唐氏症患者提早退化的原因並不清楚。這也是我們在本次研究中要探討的一個主要項目。

方法
為了瞭解唐氏症患者功能性退化的原因，我們比較目前已知造成失智症風險的APOE、ESR2、CYP17、CYP19基因中12個單核苷酸多型性(single nucleotide polymorphisms; SNPs)(rs405509、rs429358、rs7412、rs17766755、rs4365213、rs12435857、rs4986938、rs6163、rs3740397、rs10786712、rs743572、rs1870049)在唐氏症與正常人的分佈以及在失智與未失智唐氏症患者的比例異同。此外，我們亦以適應性行為量表（Adaptive Behaviour Dementia Questionnaire；ABDQ）評估唐氏症患者否發生失智症或退化性行為。我們並同時究其他相關的危險因子，包含年齡、性別、智商、行為問題有無、以及適應性行為量表與失智症的發生是否相關。

結果
我們總共邀請了23位唐氏症患者參與此研究，以及49位非唐氏症且無失智症之一般人做為對照組。我們收集了總共72個檢體進行12個SNPs的基因型分析。結果顯示，唐氏症患者的失智症與行為問題、智能障礙程度、適應性行為量表分數在統計學上有顯著的相關性。智商較低以及有行為問題的唐氏症患者與失智症有著高度相關性(皆為p<0.001 )。同時我們也先分析了SNP與失智症之間的關係，將患有失智症的唐氏症患者與SNPs做評估，發現APOE

Background
Down syndrome (DS) is one of the most common mental retardation chromosomal disorder in Taiwan. Even though our healthcare system encourages Down syndrome screen，there is still a number of babies with DS delivered. DS babies will have be problems congenital anomalies and need to be paid more attention in education. When turning into adulthoods, early degeneration is a major concern, such as dementia. The cause of dementia in DS is not well delineated. In this study, we would like to evaluate the role of single nucleotide polymorphism (SNPs) in DS with dementia.

Method
We compared the percentage of several SNPs in DS with and without dementia, including 12 SNPs in APOE、ESR2、CYP17 and CYP19 genes (rs405509, rs429358, rs7412, rs17766755,rs4365213, rs12435857, rs4986938, rs6163,rs3740397,rs10786712,rs743572, and rs1870049). ABDQ (Adaptive Behaviour Dementia Questionnaire) scores, age, sex, IQ, and behavior problems were also analyzed.

Result
Total 23 DS subjects and 49 healthy subjects were analyzed. The dementia in DS is positively correlated with behavioral problems, IQ, ABDQ scores (p<0.001). In addition, APOE

口試委員會審定書 V
致謝 VI
中文摘要 1
英文摘要 3
第一章 研究背景 4
1-1 唐氏症與老化 4
1-2 失智症致病因子研究現況 4
1-3 唐氏症患者失智因子的研究 6
第二章 研究動機 8
第三章 研究目的 8
第四章 研究方法 8
4-1 收集個案 8
4-1-1 病患來源 8
4-1-2 對照組 9
4-1-3 臨床評估 9
4-1-4 檢體收集 9
4-2 檢體處理及檢測 9
4-2-1 血液檢體DNA萃取流程 9
4-2-2 基因型鑑定 10
4-2-2-1 TaqMan probe genotyping原理 11
4-2-2-2 材料 11
4-2-2-3 實驗步驟 11
4-3 資料分析與判讀 12
4-4 統計 12
第五章 結果 13
5-1 受試者分析 13
5-2 失智症與危險因子相關性分析 13
5-2-1 APOE基因分型分析結果 13
5-2-2 ESR2基因分型分析結果 15
5-2-3 CYP17基因分型分析結果 15
5-2-4 CYP19 基因分型分析結果 16
5-3 卡方分析 17
第六章 討論 17
6-1 台灣唐氏症失智症患者基因型特性 17
6-2 國外研究結果比較 17
6-2-1 APOE基因型 17
6-2-2 ESR2基因型 18
6-2-3 CYP17基因型 18
6-2-4 CYP19基因型 19
6-3 研究限制 19
6-3-1 個案數 19
6-3-2 個案狀況評估 19
6-3-3 結果判讀 20
6-3-4 統計分析 20
6-4 未來的方向 21
第七章 參考文獻 22

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