Bioinformatics Analysis Of Potential Genes And Functional Pathways Of Fibromyalgia And Its Migraine Comorbidity

Background and objectiveFibromyalgia(FM)often occurs in middle-aged women.The population prevalence rate is about 2-4%.The pathogenesis of FM is still controversial,and the therapeutic effects of current therapies are still far from satisfactory.FM patients may be complicated by migraine,irritable bowel syndrome,and depression,which seriously affect work and life,and cause huge economic losses to society.The prognosis of fibromyalgia migraine comorbidity(FMMC)seemed to be worse.We aimed to explore genes and pathways in the pathogenesis of FM and FMMC by bioinformatics analysis.Materials and MethodsBased on the FM and normal control blood sample chip datasets(GSE67311,GSE65033),we analyzed and found differentially expressed genes(DEG)and mi RNA(DEM)between the two groups.Pathway analysis and gene set enrichment analysis(GSEA)were carried out.Target genes were predicted in mi RNet database.FM-related genes were obtained from the Comparative Toxicology Genomics Database(CTD).Protein-protein interaction(PPI)network was constructed and key modules were identified.Hub genes and candidate genes were identified based on DEGs,genes predicted by mi RNAs,FM-related genes in CTD and key modules.In additon,the correlation between candidate genes and musculoskeletal diseases,mental disorders,immune system diseases were analyzed in CTD.Treatment related genes of the commonly used therapeutic drugs such as pregabalin,milnacipran,and amitriptyline were analyzed.The expression of genes in brain cells were analyzed.Finally,fibromyalgia related mi RNA-m RNA regulatory networks were constructed.Similarly,30 cases of FMMC and 31 cases of migraine-free data from the blood samples of 61FM patients in the GSE67311 dataset were selected.FMMC related genes were identified based on weighted gene co-expression network analysis(WGCNA).The correlations between genes and migraine were analyzed in CTD.The enrichment pathways related to FMMC were analyzed.ResultsA total of 1499 genes were differentially expressed in the FM group of the GSE67311 dataset(P<0.05).102 genes were up-regulated and 46 down-regulated according to the threshold|log₂FC|>0.2.In the FM group of the GSE65033 dataset,206mi RNAs were down-regulated and 15 were up-regulated(P<0.05,|log₂FC|>1).DEGs were enriched in erythrocyte differentiation,positive regulation of leukocyte degranulation,immune system development,ion homeostasis,immunoglobulin receptor activity.GSEA analysis showed that GO?GLIAL?CELL?ACTIVATION,KEGG?TGF?BETA?SIGNALING?PATHWAY items were enriched.A total of 109target genes were predicted by the up-regulated mi RNA hsa-mi R-19a-5p.CD38,GATM,HDC,and FOS were selected as candidate genes.CTD analysis found that candidate genes were related to fibromyalgia,sleep disorders,depression,immune system diseases.Brain cell expression localization analysis found that CD38 and FOS were mainly expressed in astrocytes,GATM and HDC were mainly localized in microglia.CTD analysis found genes related to the potential effects of commonly used therapeutic drugs such as pregabalin,milnacipran,and amitriptyline,for FM.At the same time,it was found that there was a partial overlap between the therapy-related genes and FM-related genes of the drug metformin,which has the potential to treat a variety of diseases.Finally,the potential mi RNA-m RNA regulatory network for fibromyalgia was successfully constructed,such as hsa-mi R-126-5p/GATM,hsa-mi R-19a-5p/CD38.136 genes in the FMMC group were up-regulated(P<0.05).FMMC-related module genes were enriched in cellular polysaccharide metabolic process,voltage-gated calcium channel activity,Renin-angiotensin system,MAPK signaling pathway,Chemokine signaling pathway.9 key genes including AGTR1 and WASL were screened.ConclusionsBioinformatics analysis is conducive to the study of the pathogenesis of FM and FMMC.We found DEGs and DEMs between the blood of FM and the normal control group.Some genes and functional pathways related to FM were found.In addition,candidate genes CD38,GATM,HDC,FOS were identified.Compared with patients without migraine comorbidity,FMMC patients have DEGs and functional enrichment items.The role of GTR1,WASL in the potential pathogenesis of FMMC is worthy of in-depth exploration.