Identification of common susceptibility genes and drug target genes in multiple sclerosis, systemic lupus erythematosus, and rheumatoid arthritis and its value to guide clinical treatment

Abstract

Background: Multiple sclerosis (MS) is an autoimmune-mediated demyelinating disease of the white matter in the central nervous system (CNS). In clinical practice, it was found that MS is associated with a variety of autoimmune diseases, such as systemic lupus erythematosus (SLE), rheumatoid arthritis (RA). The aim of this study was to identify common susceptibility genes and drug target genes in MS, SLE, and RA and to provide new insights into treatment.

Methods: The common susceptibility genes of MS, SLE, and RA were obtained by searching the GWAS database and using microarray data to validate. The Genome Ontology (GO) and the Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses were performed, and the common KEGG pathways were selected. All the genes enriched in the common pathways were obtained and intersected with the susceptibility genes of MS, SLE, and RA to obtain the pathway genes of them respectively, and found the common pathogenesis-related genes of the three diseases. By reviewing the literature and the DrugBank database, the drugs and drug target genes that have been approved for the treatment of the three diseases were obtained. Finally, the DGIdb database was searched to predict potential drugs or molecular compounds that interact with susceptibility genes common to MS, SLE, and RA.

Results: In MS, SLE, and RA, there were 46 common susceptibility genes, of which 23 were significantly differentially expressed in the microarray expression profile. Then, 2117 genes were obtained in the 42 common pathways, among which 17 pathogenesis-related genes were common in MS, SLE, and RA. The Drugbank database was used to obtain 29 drug target genes for MS, 43 drug target genes for RA, and 20 drug target genes for SLE. DHODH is a common drug target gene for MS, SLE, and RA, and its corresponding drugs are Leflunomide and Teriflunomide. A total of 13 genes and 366 potential drugs or molecular compounds were predicted to have interaction relationships after searching the DGIdb database.

Conclusion: The common susceptibility genes and drug target genes among MS, SLE, and RA provide a theoretical basis for the co-morbidity phenomenon of the three diseases in clinical practice and may guide the clinical treatment.

Keywords: Common susceptibility genes; Drug target genes; Multiple sclerosis; Pathogenesis-related genes; Rheumatoid arthritis; Systemic lupus erythematosus.