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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