Understanding gene expression in coronary artery disease through global profiling, network analysis and independent validation of key candidate genes

生物 基因表达谱 基因 转录组 微阵列分析技术 微阵列 折叠变化 基因表达 小桶 CXCL1型 基因调控网络 免疫系统 遗传学 计算生物学 生物信息学 趋化因子
作者
Prathima Arvind,Jayashree Shanker,Srikarthika Jambunathan,Jiny Nair,Vijay V. Kakkar
出处
期刊:Journal of Genetics [Springer Nature]
卷期号:94 (4): 601-610 被引量:17
标识
DOI:10.1007/s12041-015-0548-3
摘要

Molecular mechanism underlying the patho-physiology of coronary artery disease (CAD) is complex. We used global expression profiling combined with analysis of biological network to dissect out potential genes and pathways associated with CAD in a representative case-control Asian Indian cohort. We initially performed blood transcriptomics profiling in 20 subjects, including 10 CAD patients and 10 healthy controls on the Agilent microarray platform. Data was analysed with Gene Spring Gx12.5, followed by network analysis using David v 6.7 and Reactome databases. The most significant differentially expressed genes from microarray were independently validated by real time PCR in 97 cases and 97 controls. A total of 190 gene transcripts showed significant differential expression (fold change>2,P<0.05) between the cases and the controls of which 142 genes were upregulated and 48 genes were downregulated. Genes associated with inflammation, immune response, cell regulation, proliferation and apoptotic pathways were enriched, while inflammatory and immune response genes were displayed as hubs in the network, having greater number of interactions with the neighbouring genes. Expression of EGR1/2/3, IL8, CXCL1, PTGS2, CD69, IFNG, FASLG, CCL4, CDC42, DDX58, NFKBID and NR4A2 genes were independently validated; EGR1/2/3 and IL8 showed >8-fold higher expression in cases relative to the controls implying their important role in CAD. In conclusion, global gene expression profiling combined with network analysis can help in identifying key genes and pathways for CAD.
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