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. 2023 Feb 18;24(4):4124.
doi: 10.3390/ijms24044124.

Analysis of the Genetic Relationship between Atherosclerosis and Non-Alcoholic Fatty Liver Disease through Biological Interaction Networks

Francisco Andújar-Vera  1   2   3   4 , María Ferrer-Millán  1 , Cristina García-Fontana  1   2   5 , Beatriz García-Fontana  1   2   6 , Sheila González-Salvatierra  1   5   7 , Raquel Sanabria-de la Torre  1   8 , Luis Martínez-Heredia  1 , Blanca Riquelme-Gallego  1   9 , Manuel Muñoz-Torres  1   2   5   7
Affiliations

Analysis of the Genetic Relationship between Atherosclerosis and Non-Alcoholic Fatty Liver Disease through Biological Interaction Networks

Francisco Andújar-Vera et al. Int J Mol Sci. .

Abstract

Non-alcoholic fatty liver disease (NAFLD) seems to have some molecular links with atherosclerosis (ATH); however, the molecular pathways which connect both pathologies remain unexplored to date. The identification of common factors is of great interest to explore some therapeutic strategies to improve the outcomes for those affected patients. Differentially expressed genes (DEGs) for NAFLD and ATH were extracted from the GSE89632 and GSE100927 datasets, and common up- and downregulated DEGs were identified. Subsequently, a protein-protein interaction (PPI) network based on the common DEGs was performed. Functional modules were identified, and the hub genes were extracted. Then, a Gene Ontology (GO) and pathway analysis of common DEGs was performed. DEGs analysis in NAFLD and ATH showed 21 genes that were regulated similarly in both pathologies. The common DEGs with high centrality scores were ADAMTS1 and CEBPA which appeared to be down- and up-regulated in both disorders, respectively. For the analysis of functional modules, two modules were identified. The first one was oriented to post-translational protein modification, where ADAMTS1 and ADAMTS4 were identified, and the second one mainly related to the immune response, where CSF3 was identified. These factors could be key proteins with an important role in the NAFLD/ATH axis.

Keywords: atherosclerosis; non-alcoholic fatty liver disease; protein–protein interaction network.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Panels (A,B) show volcano plot with DEGs identified in NAFLD and ATH, respectively (|log2 FC (fold change)|> 1 and adj. p-value < 0.05). Panels (C,D) show a list with common down- and up-regulated DEGs identified in both pathologies, respectively.
Figure 2
Figure 2
Analysis of the PPI network of DEGs. Panel (A) shows PPI network constructed with 21 common proteins between NAFLD and ATH. Panel (B) shows the PPI network modules identified using the MCODE plug-in.
Figure 3
Figure 3
Main enrichment results of module 1 (A) and module 2 (B). The size of dots corresponds to the number of genes while the color of dots denotes the False Discovery Rate (FDR) value. The shapes of the dots in the Gene Ontology enrichment refer to Biological Process (BP), Molecular Function (MF), and Cellular Component (CC).
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