GSTCD基因表达调控及其与慢性阻塞性肺疾病相关性研究

项目名称： GSTCD基因表达调控及其与慢性阻塞性肺疾病相关性研究

项目编号： No.31200940

项目类型： 青年科学基金项目

立项/批准年度： 2013

项目学科： 遗传学与生物信息学、细胞生物学

项目作者： 钟丽

作者单位： 云南大学

项目金额： 22万元

中文摘要： 慢性阻塞性肺疾病(COPD)是一种以肺功能下降为特征的呼吸系统疾病。近期全基因组关联分析研究(GWAS)揭示位于4q24区段的GSTCD基因突变rs10516526与肺功能及COPD显著相关。我们推测GSTCD上rs10516526位点或其他与之连锁的位点，通过增强子模式调控该基因表达，从而影响肺功能及COPD的发生或发展。为此，本研究拟使用荧光定量PCR技术分析COPD疾病组和对照组支气管上皮组织中GSTCD基因的表达差异；分析千人基因组计划数据以寻找与rs10516526连锁的位点为潜在功能性位点；通过染色体捕获技术、荧光素酶法及染色质免疫沉淀等试验，鉴别可调控GSTCD基因表达的增强子及功能性位点，及该位点发挥作用的分子机制。本项目对于探讨COPD发病的分子机制和防治策略具有重要的意义，同时为整合GWAS研究结果、生物信息学、功能基因组学等手段研究复杂疾病机理提供一个良好的范例。

中文关键词： 慢性阻塞性肺疾病；GSTCD；基因表达调控；SNP位点；

英文摘要： Chronic obstructive pulmonary disease (COPD), is a kind of common respiratory diseases characterized by lung function declined. Recent genome-wide association studies (GWAS) of COPD have suggested that one SNP (rs10516526) in glutathine s-transferase, c-terminal domain (GSTCD), is associated with lung function (measured by forced expiratory volume in one second, FEV1) and COPD. We hypothesized that this SNP, or the ones in linkage disequilibrium (LD) with it, could regulate GSTCD gene expression through enhancer model, and further contribute to COPD onset. In this project,we will measure the gene expression by real-time PCR in cases and controls in lung bronchial epithelial tissues. Then we will analyze 1000 genomes data to obtain the SNPs in strong LD with rs10516526, which will be potential causal ones. For the regions where they locate, we will use chromosome conformation capture to investigate the interaction between these regions and GSTCD promoter, in order to determine the real enhancer region. Moreover, we will use luciferase assay to compare the enhancer activity between two alleles and chromatin immunoprecipitation to identify the transcript factor that bind to this region. This project will shed more light on the molecular mechanism of COPD onset and provide an ideal example on how to combine GWAS res

英文关键词： Chronic obstructive pulmonary disease；glutathione S-transferase; c-terminal domain；gene expression and regulation；Single nucleotide polymorphism；