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研究生:蔡麗忍
研究生(外文):Li-Jen Tsai
論文名稱:台灣地區華人的紅斑性狼瘡致病基因探討
論文名稱(外文):Genomic and molecular genetic study of systemic lupus erythematosus in a Chinese population in Taiwan
指導教授:蔡麗敏蔡麗敏引用關係蔡肇基蔡肇基引用關係
指導教授(外文):Lih-Min TsaiJaw-Ji Tsai
學位類別:博士
校院名稱:國防醫學院
系所名稱:生命科學研究所
學門:生命科學學門
學類:生物學類
論文種類:學術論文
論文出版年:2006
畢業學年度:95
語文別:中文
論文頁數:129
中文關鍵詞:紅斑性狼瘡個案與對照組相關性分析家族式相關性分析發炎自體抗體
外文關鍵詞:Systemic lupus erythematoususcase-control association studyfamily-based association studyinflammationauto-antibodies
相關次數:
  • 被引用被引用:1
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  • 下載下載:102
  • 收藏至我的研究室書目清單書目收藏:2
紅斑性狼瘡(Systemic lupus erythematousus, SLE)是一種複雜的多基因遺傳因子疾病。我們的實驗策略是挑選候選基因(candidate gene)並採用個案與對照組相關性分析(case-control association study) ,接著採用家族式相關性分析(family-based association study) 。候選基因的挑選條件有二,其一是根據它的發炎(inflammation)特徵去挑選發炎介質(cytokine)。其次是根據它的自體抗體(auto-antibodies) 的產生及清除去挑選。我們總計挑選了包括IL1-b和IL1RN和LTA和TNF-α等十一個候選基因。為了簡化紅斑性狼瘡的複雜病症,並且強化我們的遺傳研究結果,避免因紅斑性狼瘡的複雜而遺漏有可能是致病基因的候選基因,我們選擇了墨西哥簡化的紅斑性狼瘡的疾病活動係數(MEX-SLEDAI)量表來進行病症及基因型的相關性研究。我們的結果顯示利用MEX-SLEDAI量表將紅斑性狼瘡病患群一分為二,可以發現候選基因IL1-b和IL1RN和LTA和TNF-α的分子機制牽涉到紅斑性狼瘡的病理機轉。在使用反轉錄酶聚合酶連鎖反應(RT-PCR)決定IL1RN的各式各樣傳訊RNA (mRNA isoforms) 表現型態時,我們發現紅斑性狼瘡病患IL1RN的mRNA isoforms表現型態與正常人不同─病患有的是多了四號isoform;有的是一號isoform表現的少些。這不同的表現型態可能由於alternative splicing的活性不同所致 。
SLE is a complex disease for which many susceptibility loci have been identified. Our strategy is to use candidate gene case-control association study, and then followed by a family-based association study. The criteria for the selection of candidate genes include two: 1. Depend on inflammation symptoms. 2. Depend on the auto-antibodies generation and clean-up. We have selected 11 candidate genes including IL1RN, IL1-b, TNF-α, LTA, etc. To simplify the phenotype and stratify our genotype result, we use MEX-SLEDAI score to correlate the genotype and phenotype. After our study we have known that the SLE disease activity index could simplify the phenotype and stratify the genetic approach in genetic study of SLE. Use this tree model, we have found candidate genes, IL1RN, IL1-b, TNF-α, LTA, their molecular mechanism involved in this disease. Using RT-PCR to determine the expression pattern of IL1RN isoforms, we found different expression patterns between normal controls and SLE patients, with an addition of IL1RN isoform 4 or the low expression of IL1RN isoform 1. This different expression patterns may depend on different alternative splicing activity.
總目錄
頁次
正文目錄‧‧‧‧‧‧‧‧‧‧‧‧‧‧‧‧‧‧‧‧‧‧‧‧II
表目錄‧‧‧‧‧‧‧‧‧‧‧‧‧‧‧‧‧‧‧‧‧‧‧‧‧VI
圖目錄‧‧‧‧‧‧‧‧‧‧‧‧‧‧‧‧‧‧‧‧‧‧‧‧VII
中文摘要‧‧‧‧‧‧‧‧‧‧‧‧‧‧‧‧‧‧‧‧‧‧‧VIII
英文摘要‧‧‧‧‧‧‧‧‧‧‧‧‧‧‧‧‧‧‧‧‧‧‧‧IX
簡寫表‧‧‧‧‧‧‧‧‧‧‧‧‧‧‧‧‧‧‧‧‧‧‧‧‧X
第一章 緒論‧‧‧‧‧‧‧‧‧‧‧‧‧‧‧‧‧‧‧‧‧‧1
第二章墨西哥簡化的紅斑性狼瘡的疾病活動係數(Mexican Modification of the Systemic Lupus Erythematosus Disease Activity Index)量表在遺傳研究的應用‧‧‧‧‧‧‧10
第三章 發炎介質IL1RN的傳訊RNA在紅斑性狼瘡的不同表現型式‧‧‧‧‧‧‧‧‧‧‧‧‧‧‧‧‧‧‧‧‧‧36
第四章 總結論‧‧‧‧‧‧‧‧‧‧‧‧‧‧‧‧‧‧‧‧‧58
附錄‧‧‧‧‧‧‧‧‧‧‧‧‧‧‧‧‧‧‧‧‧‧‧‧‧‧89
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