Bioinformatics assessment of PPARγ role in regulation of gene networks expression involved in congenital heart disease

Introduction & Objectives: Congenital heart diseases impose a huge burden on societies, but the mechanisms for their pathogenesis and control in gene expression context are not well understood. The role of PPARγ transcription factor in the differentiation and development of many tissues and cardiovascular disease has been identified. But the mechanism of its effect is not known.Materials & Methods: In this study, microarray data on congenital heart disease at the GEO database were analyzed by R software and genes with significant differential expression (P<0.05) were candidate for investigation of presence of PPARγ response elements known as PPRE. Protein interactions of these genes were analyzed in Cytoscape software. Also, 20 genes with the highest average interaction score (minimum confidence = 0.4) were predicted in the constructed network and enrichment of these genes was studied at Gene Ontology database.Results: Of the 1802 genes that showed expression alteration in congenital heart disease, 8 genes including PGK1, PKM, BCL2, GHITM, VEGFA, SLC9A1, CAT and TNFSF10 had PPRE elements in their promoter and their interaction with genes involved in biological processes including Regulation of cell death, Regulation of metabolic process, Anatomical structure development and Cell differentiation was identified.Conclusion: The genes found in this study are associated with processes related to development, differentiation, regulation of cell death and regulation of cellular metabolic processes. These processes play a key role in the development of congenital heart disease. On the other hand, the expression of these genes is potential of being regulated by the PPARγ. So PPARγ can be proposed as a potential factor in regulating key processes of congenital heart disease and identifying its potential value in Diagnosis and treatment of these abnormalities, especially in the embryonic period, is suggested for experimental study.

کلیدواژه ها:

Congenital heart disease ، PPARγ ، PPRE ، Gene Ontology ، expression network