Network-medicine approach for the identification of genetic association of parathyroid adenoma with cardiovascular disease and type-2 diabetes

• DOI: 10.1093/bfgp/elac054
• Publication Date: 2023-02-15T15:47:33Z
• Authors: Nikhat Imam; Aftab Alam; Mohd Faizan Siddiqui; Akhtar Veg; Sadik Bay; Md Jawed Ikbal Khan; Romana Ishrat
• Keywords: Drug repositioning; FLNA; Interactome; Repurposing; Interaction network; Genetic Association

Abstract Primary hyperparathyroidism is caused by solitary parathyroid adenomas (PTAs) in most cases (⁓85%), and it has been previously reported that PTAs are associated with cardiovascular disease (CVD) type-2 diabetes (T2D). To understand the molecular basis of PTAs, we have investigated genetic association amongst CVD T2D through an integrative network-based approach observed a remarkable resemblance. The current study proposed to compare PTAs-associated proteins overlapping determine relationship. We constructed protein–protein interaction network integrating curated experimentally validated interactions humans. found $11$ highly clustered modules network, which contain total $13$ hub (TP53, ESR1, EGFR, POTEF, MEN1, FLNA, CDKN2B, ACTB, CTNNB1, CAV1, MAPK1, G6PD CCND1) commonly co-exist CDV reached network’s hierarchically modular organization. Additionally, implemented gene-set over-representation analysis over biological processes pathways helped identify disease-associated prioritize target proteins. Moreover, identified respective drugs these built bipartite helps decipher drug–target interaction, highlighting influential roles on apparently unrelated targets pathways. Targeting using drug combinations or drug-repurposing approaches will improve clinical conditions comorbidity, enhance potency few give synergistic effect better outcomes. This opens new horizon for more personalized treatment opportunities investigate multi-drug may be helpful further mechanisms underlying PTA diseases.