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

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Abstract

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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Acknowledgements

This work was supported by the Thrombosis Research Institute, London; the Department of Biotechnology, Ministry of Science and Technology, Government of India (grant number BT/01/CDE/08/07); the Tata Social Welfare Trust, India (grant number TSWT/IG/SNB/ JP/Sdm); Weston foundation, UK and Foundation Bey, Switzerland. We thank all the clinical investigators, staff, administrative teams and participants of the IARS from Narayana Hrudayalaya, Bengaluru and Asian Heart Centre, Mumbai for their valuable contributions. Vinoth Kumar G., BE Computer Science (Thrombosis Research Institute, India) provided assistance in preparing the tables and figures. S. A. Deepak Ph.D. and Nilanjan Guha Ph.D. (Ms.Agilent Technologies) provided support in the experimental set up.

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  1. Mary and Garry Weston Functional Genomics Unit, Thrombosis Research Institute, Bengaluru, 560 099, India

    PRATHIMA ARVIND, SHANKER JAYASHREE, SRIKARTHIKA JAMBUNATHAN, JINY NAIR & VIJAY V. KAKKAR

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  1. PRATHIMA ARVIND
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  2. SHANKER JAYASHREE
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Correspondence to SHANKER JAYASHREE.

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[Arvind P., Jayashree S., Jambunathan S., Nair J. and Kakkar V. V. 2015 Understanding gene expression in coronary artery disease through global profiling, network analysis and independent validation of key candidate genes. J. Genet. 94, xx–xx]

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ARVIND, P., JAYASHREE, S., JAMBUNATHAN, S. et al. Understanding gene expression in coronary artery disease through global profiling, network analysis and independent validation of key candidate genes. J Genet 94, 601–610 (2015). https://doi.org/10.1007/s12041-015-0548-3

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