研究生: |
賴怡君 Yi-Chun Lai |
---|---|
論文名稱: |
KLK1、TIEG1/EGR alpha、TNF-alpha、IL-1 alpha及IL-1 beta基因多型性與原發性膀胱輸尿管逆流疾病發生及腎病進行的相關性研究 Association of KLK1, TIEG1/EGR alpha, TNF-alpha, IL-1 alpha and IL-1 beta Gene Polymorphisms with Primary VUR Development and Progression |
指導教授: |
李桂楨
Lee, Guey-Jen |
學位類別: |
碩士 Master |
系所名稱: |
生命科學系 Department of Life Science |
論文出版年: | 2004 |
畢業學年度: | 92 |
語文別: | 中文 |
論文頁數: | 65 |
中文關鍵詞: | 基因多型性 、原發性膀胱輸尿管逆流 、疾病發生 、腎病進行 、腫瘤壞死因子 、介白素1 |
英文關鍵詞: | Gene Polymorphism, Primary VUR, disease development and progression, KLK1, TIEG1, EGR alpha, TNF-alpha, IL-1 |
論文種類: | 學術論文 |
相關次數: | 點閱:233 下載:2 |
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膀胱輸尿管逆流(VUR)為常見的小兒先天性泌尿道疾病,部份與家族性遺傳相關,但目前致病之基因仍不明確,且VUR孩童的疾病進展或預後情況不一,嚴重者會進入末期腎病(ESRD)。本研究即在探討人類腎臟KLK1、TIEG1/EGR、TNF-、IL-1、IL-1基因的多型性與台灣孩童VUR發生及腎病進行的相關性。KLK1的啟動子中-130 GN多型性係藉genotyping、SSCP及allele-specific PCR來分析基因型。TIEG1/EGR基因經由直接定序及比對,找出兩個尚未報導過的多型點:EGR啟動子上的C-1445G,及兩基因共用的第三外顯子上的T216 (A>C),此二多型性點與TNF-的C-863A、C-857T及IL-1的C-889T、IL-1的C-511T皆藉由限制酶切割PCR放大片段來分析基因型,另IL-1的3'UTR多型性則利用SSCP的方式區分基因型。結果顯示EGR的-1445C與VUR疾病的發生有關,而與腎病進行有相關的多型性則有兩個,分別為KLK1的啟動子的-130 GN多型性的K對偶基因及TNF-的-863A多型性,其他多型性則未發現與VUR疾病的發生或腎病進行有關。本實驗尚有做KLK1及EGR啟動子多型性轉錄活性分析,以報導基因luciferase於HEK-293細胞株中進行基因表現,結果顯示KLK1 -130 GN多型性的K對偶基因及EGR多型性的G對偶基因有較低的轉錄活性。
Vesicoureteral reflux (VUR) is a common pediatric disease. The development of VUR is highly familially inherited and the disease progression is variable. Some patients may lead to severe end-stage renal disease (ESRD). In this study, polymorphisms of human renal kallikrein gene (KLK1), TGFβ-inducible early gene 1/early growth response gene (TIEG1/EGR), tumor necrosis factor- gene (TNF-), interleukin-1 gene (IL-1), interleukin-1 gene (IL-1) were evaluated for the association with VUR development and progression in Taiwanese children. The KLK1 promoter -130 GN polymorphism was analyzed by genotyping, single-strand conformation polymorphism (SSCP) analysis, and allele-specific polymerase chain reaction (PCR). By PCR and direct sequencing, two new polymorphisms, C-1445G in the EGR promoter region and T216 (A>C) in the exon 3 of the TIEG1 gene were identified and analysed. Both polymorphisms as well as TNF- C-863A and C-857T, IL-1 C-889T, and IL-1 C-511T polymorphisms were analyzed by restriction enzyme digestion of PCR products. IL-1 3'UTR polymorphism was analyzed by SSCP. Among these eight polymorphisms studied, EGR C-1445G showed association with VUR development, whereas KLK1 -130 GN and TNF- C-863A polymorphisms with VUR progression. The fragments containing KLK1 -130 GN and EGR C-1445G polymorphisms were fused to a firefly luciferase reporter and transiently expressed in HEK-293 cells. Significant lower transcriptional activity was observed with -130 G12 K allele and EGR -1445 G allele.
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