Pathway-based gene-gene interaction network modelling to predict potential biomarkers of essential hypertension

摘要

Essential hypertension (EH) is a major risk factor for cardiovascular disease. Despite considerable efforts to elucidate the pathogenesis of EH, there is an imperious need for novel indicators of EH. This study aimed to develop a method to predict potential biomarkers of EH from the point of view of network. A pathway-based gene-gene interaction (GGI) network model was constructed and analyzed, containing 116 nodes and 1272 connections. The nodes represented EH-related genes, and that connections represented their interactions. The network showed a small-world property and uneven degree distribution, suggesting that a few highly interconnected hubs played a vital role in EH. An inherent hierarchy and assortative mixing pattern were also observed in the network. GNAS, GNB3, PF4 and PPBP showed the highest values of degrees and centrality indices, and were chosen as potential biomarkers of EH. A two-mode network model based on the potential biomarkers demonstrated that hemostasis and GPCR ligand binding pathway were key pathways contributing to EH. Results of this study improve our current understanding of the molecular mechanisms driving EH. The selected genes and pathways have the potential to be used in the diagnosis and treatment of EH. Moreover, the combination of pathway analysis and complex network methodology provides a novel strategy for searching new genetic indicators of complex diseases.