Identification of Gene Networks Related to the F2 Gene in Arterial Thrombogenesis Modulation

Abstract

Introduction: Arterial thrombogenesis is a phenomenon caused by endothelial dysfunction, genetic interactions, and transcriptional regulation, which are essential to understanding the clinical consequences of ischemic vessel obstruction. Among the molecular components that promote thrombogenesis are the c.1621 C>T/p.R541W and G20210A variations related to the F2 gene. However, their role is not yet fully understood, despite studies suggesting that these variations could pose a risk for atherosclerotic cardiovascular diseases.

Objective: Using bioinformatics resources, we aimed to identify the transcription factors that regulate the expression of the F2 gene and their interaction with gene networks involved in arterial thrombogenesis modulation.

Methods: To identify the transcription factors of the F2 gene, we visited the www.genecards.org website, which provided genocentric information, and we conducted a search on various databases (HNGC, Gene, Ensembl, OMIM, UniProtKB). Subsequently, we identified the binding sites of the most relevant transcription factors in the predicted gene promoter. An integrated analysis was performed using a gene interaction network (co-expression, physical interactions, genetic interactions, co-localization, etc.) with the Genemania plugin.

Results: We observed co-expression of F2 and AHR, suggesting that AHR is directly stimulated by cytoplasmic signals, and when activated, it regulates gene expression in the cell nucleus. Furthermore, studies demonstrate that apart from its transcriptional functions, AHR mediates protein degradation through the ubiquitin-ligase complex, enhancing thrombosis.

Conclusion: This study presents, for the first time, the co-expression network of AhR with F2, which may be associated with atherosclerosis development. This finding could assist clinicians in understanding the cause of arterial thrombogenesis.