title: Understanding gene expression in coronary artery disease through global profiling, network analysis and independent validation of key candidate genes.
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.
authors.affiliation: Mary and Garry Weston Functional Genomics Unit, Thrombosis Research Institute, Bengaluru 560 099, India. jayashreeshanker@triindia.org.in.
authors.forename: Prathima
authors.initials: P
authors.lastname: Arvind
authors.forename: Shanker
authors.initials: S
authors.lastname: Jayashree
authors.forename: Srikarthika
authors.initials: S
authors.lastname: Jambunathan
authors.forename: Jiny
authors.initials: J
authors.lastname: Nair
authors.forename: Vijay V
authors.initials: VV
authors.lastname: Kakkar
mesh_terms: D016022:Case-Control Studies; D003324:Coronary Artery Disease / Q000235:genetics*; D005260:Female; D015870:Gene Expression / Q000235:genetics*; D020869:Gene Expression Profiling / Q000379:methods; D006801:Humans; D008297:Male; D008875:Middle Aged