Department of Pediatric Cardiology, Sichuan University, Sichuan, People's Republic of China.
Eur Rev Med Pharmacol Sci. 2012 Dec;16(14):1961-6.
Asthma is a disease resulting from a complex interaction of multiple genetic and environmental factors. More than 200 asthma candidate genes have been identified in the past decades by using genetic association studies, positional cloning and knockout mouse approaches.
This study was to identify differentially expressed genes and provide direction for medicine design related to pediatric allergic asthma with DNA microarray.
The gene expression profile of pediatric allergic asthma GSE18965 was downloaded from Gene Expression Omnibus database which includes 16 samples, 7 normal and 9 pediatric allergic asthma samples. The differentially expressed genes between normal and disease samples were identified by using R language. The co-expression coefficient was calculated among the differentially expressed genes to construct co-expression networks with String Software. Software DAVID and FuncAssociate were used to analyze the functions of genes in the co-expression networks.
A total of 133 genes were identified as differentially expressed genes between normal and disease samples, and 8 related small medicine molecules were also obtained (penbutolol, felbinac, iodixanol, josamycin, oxolamine, 3-nitropropionic acid, scriptaid, and sanguinarine) from database CMAP. The differentially expressed genes were enriched in several biological processes, in which viral transcription and lysosome were the most significant GO term of up- or down-regulated genes.
Our present findings shed new light on the molecular mechanism of allergic asthma and provide three small molecular medicines (3-nitropropionic acid, scriptaid, and sanguinarine) which have the potential to use in clinic for treatment of allergic asthma in future.
哮喘是一种由多种遗传和环境因素复杂相互作用引起的疾病。在过去的几十年中,通过遗传关联研究、定位克隆和敲除小鼠方法,已经确定了 200 多个哮喘候选基因。
本研究旨在使用 DNA 微阵列鉴定差异表达基因,并为儿科过敏性哮喘的药物设计提供方向。
从基因表达综合数据库(GEO)中下载儿科过敏性哮喘 GSE18965 的基因表达谱,该数据库包含 16 个样本,7 个正常样本和 9 个儿科过敏性哮喘样本。使用 R 语言识别正常和疾病样本之间的差异表达基因。使用 String 软件计算差异表达基因之间的共表达系数,构建共表达网络。使用 DAVID 和 FuncAssociate 软件分析共表达网络中基因的功能。
共鉴定出 133 个正常和疾病样本之间差异表达的基因,还从数据库 CMAP 中获得了 8 种相关的小分子药物(普萘洛尔、非诺洛芬、碘海醇、交沙霉素、奥洛胺、3-硝基丙酸、scriptaid 和血根碱)。差异表达基因富集在几个生物学过程中,其中病毒转录和溶酶体是上调或下调基因最显著的 GO 术语。
我们的研究结果为过敏性哮喘的分子机制提供了新的认识,并为未来治疗过敏性哮喘提供了三种有潜力用于临床的小分子药物(3-硝基丙酸、scriptaid 和血根碱)。