Kong Qian, Li Wen-Jing, Huang Hua-Rong, Zhong Ying-Qiang, Fang Jian-Pei
Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University , Guangzhou, Guangdong , P.R. China .
J Asthma. 2015 May;52(4):343-52. doi: 10.3109/02770903.2014.971967. Epub 2014 Nov 6.
Asthma is a common childhood disease with strong genetic components. This study compared whole-genome expression differences between asthmatic young children and healthy controls to identify gene signatures of childhood asthma.
Total RNA extracted from peripheral blood mononuclear cells (PBMC) was subjected to microarray analysis. QRT-PCR was performed to verify the microarray results. Classification and functional characterization of differential genes were illustrated by hierarchical clustering and gene ontology analysis. Multiple logistic regression (MLR) analysis, receiver operating characteristic (ROC) curve analysis, and discriminate power were used to scan asthma-specific diagnostic markers.
For fold-change>2 and p < 0.05, there were 758 named differential genes. The results of QRT-PCR confirmed successfully the array data. Hierarchical clustering divided 29 highly possible genes into seven categories and the genes in the same cluster were likely to possess similar expression patterns or functions. Gene ontology analysis presented that differential genes primarily enriched in immune response, response to stress or stimulus, and regulation of apoptosis in biological process. MLR and ROC curve analysis revealed that the combination of ADAM33, Smad7, and LIGHT possessed excellent discriminating power.
The combination of ADAM33, Smad7, and LIGHT would be a reliable and useful childhood asthma model for prediction and diagnosis.
哮喘是一种常见的具有很强遗传因素的儿童疾病。本研究比较了哮喘幼儿与健康对照之间的全基因组表达差异，以确定儿童哮喘的基因特征。
从外周血单个核细胞（PBMC）中提取的总RNA进行微阵列分析。进行定量逆转录聚合酶链反应（QRT-PCR）以验证微阵列结果。通过层次聚类和基因本体分析对差异基因进行分类和功能表征。使用多元逻辑回归（MLR）分析、受试者工作特征（ROC）曲线分析和判别能力来筛选哮喘特异性诊断标志物。
对于变化倍数>2且p < 0.05，有758个命名的差异基因。QRT-PCR结果成功证实了阵列数据。层次聚类将29个高度可能的基因分为七类，同一簇中的基因可能具有相似的表达模式或功能。基因本体分析表明，差异基因主要富集在生物过程中的免疫反应、对压力或刺激的反应以及细胞凋亡的调节。MLR和ROC曲线分析显示，ADAM33、Smad7和LIGHT的组合具有出色的判别能力。
ADAM33、Smad7和LIGHT的组合将是一种用于预测和诊断的可靠且有用的儿童哮喘模型。
