Genome-Wide Gene Expression Profiling and Genetic Studies of Lower Extremity Varicose Vein

View Statistics Email Alert RSS Feed

Information

Details

Project title/計畫英文名

Project Number/計畫編號

MOST104-2314-B002-202

Translated Name/計畫中文名

下肢靜脈曲張之全基因表達圖譜及遺傳研究

Project Principal Investigator/計畫主持人

I-HUI WU

Funding Organization

Ministry of Science and Technology

Co-Investigator(s)/共同執行人

蔡佳醍

Start date/計畫起

01-08-2015

Expected Completion/計畫迄

12-07-2016

摘要：靜脈曲張為淺層靜脈擴張以及彎曲，其表現為臨床上最容易辨別的血管異常。對於其分子機制及其遺傳學研究上還不是很清楚。在本計劃中，我們計劃探討靜脈曲張的全基因表現變化，並嘗試找出造成靜脈曲張特定的基因/蛋白質。首先我們已經使用次世代定序（next generation sequencing) 的RNA-seq技術來研究患病和對照組的靜脈檢體中全基因組中mRNA表現的差異。目前我們已經確定了幾個有顯著促進和抑制調控的基因。在第一年，我們將以定量RT-PCR來驗證在動脈和靜脈檢體中以RNA-seq找到的基因表現的變化。在第二年，我們計劃用使用螢光發光的血管和紅血球細胞的斑馬魚模型來減低表達（knockdown)或過度表達（overexpress)這些目標基因，以了解靜脈系統的形態變化。我們也將探討這些促進或抑制的基因在培養的血管平滑肌細胞和内皮細胞經過模仿病人體内環境機械張力拉扯後的表現變化。到了第三年，靜脈曲張的遺傳關聯性研究將採用病例對照的方式進行，著重在這些所找到的目標基因在靜脈曲張中其功能及機制重要性。我們期望找到與靜脈曲張相關的目標基因，並進一步評估這些目標基因是否與疾病的嚴重程度和其它臨床因素有關。
Abstract: Varicose veins (VV) are among the most easily recognized vascular abnormalities with superficial venous tortuosity and enlargement. The molecular mechanism and genetics of VV are largely unknown. In the present project, we plan to explore the global expressional change of VV and try to identify specific genes/proteins that may play a role in the mechanism of VV. Preliminarily we have used next-generation RNA sequence (RNA seq) technology to study the global mRNA expressional change in the venous samples of diseased and control patients. We have identified several significantly up and down regulated genes. In the first year, we will validate the expressional changes of genes identified in the RNA-seq in arterial and venous samples by quantitative RT-PCR. In the second year, we plan to knockdown or overexpress these targeted genes using a zebrafish model with fluorescence emitting vasculature and red blood cells to see the morphological changes of the venous system. We will also explore the expressional changes of these up- or down-regulated genes in the cultured vascular smooth muscle cells and endothelial cells under mechanical stretch, mimicking the in vivo environment of VV. In the third year, genetic association studies of VV will be conducted using a case-control approach, focusing on the identified significant genes with functional significance and maybe mechanistically related to VV. We expect to find the true VV susceptibility gene(s) and further evaluate whether they are associated with disease severity and other clinical factors.

DSpace CRIS

Genome-Wide Gene Expression Profiling and Genetic Studies of Lower Extremity Varicose Vein

Details

Description