DNA methylation and gene expression profiles to identify childhood atopic asthma associated genes. 2021

Rui Chen, and Li-Zhen Piao, and Ling Liu, and Xiao-Fei Zhang
Department of Pediatrics, The Third Hospital of Jilin University, Changchun, 130033, Jilin, China.

BACKGROUND Asthma is a chronic inflammatory disorder of the airways involving many different factors. This study aimed to screen for the critical genes using DNA methylation/CpGs and miRNAs involved in childhood atopic asthma. METHODS DNA methylation and gene expression data (Access Numbers GSE40732 and GSE40576) were downloaded from the Gene Expression Omnibus database. Each set contains 194 peripheral blood mononuclear cell (PBMC) samples of 97 children with atopic asthma and 97 control children. Differentially expressed genes (DEGs) with DNA methylation changes were identified. Pearson correlation analysis was used to select genes with an opposite direction of expression and differences in methylation levels, and then Gene Ontology (GO) function and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis were performed. Protein-protein interaction network and miRNA-target gene regulatory networks were then constructed. Finally, important genes related to asthma were screened. RESULTS A total of 130 critical DEGs with DNA methylation changes were screened from children with atopic asthma and compared with control samples from healthy children. GO and KEGG pathway enrichment analysis found that critical genes were primarily related to 24 GO terms and 10 KEGG pathways. In the miRNA-target gene regulatory networks, 9 KEGG pathways were identified. Analysis of the miRNA-target gene network noted an overlapping KEGG signaling pathway, hsa04060: cytokine-cytokine receptor interaction, in which the gene CCL2, directly related to asthma, was involved. This gene is targeted by eight asthma related miRNAs (hsa-miR-206, hsa-miR-19a, hsa-miR-9,hsa-miR-22, hsa-miR-33b, hsa-miR-122, hsa-miR-1, and hsa-miR-23b). The genes IL2RG and CCl4 were also involved in this pathway. CONCLUSIONS The present study provides a novel insight into the underlying molecular mechanism of childhood atopic asthma.

UI MeSH Term Description Entries
D002648 Child A person 6 to 12 years of age. An individual 2 to 5 years old is CHILD, PRESCHOOL. Children
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D001249 Asthma A form of bronchial disorder with three distinct components: airway hyper-responsiveness (RESPIRATORY HYPERSENSITIVITY), airway INFLAMMATION, and intermittent AIRWAY OBSTRUCTION. It is characterized by spasmodic contraction of airway smooth muscle, WHEEZING, and dyspnea (DYSPNEA, PAROXYSMAL). Asthma, Bronchial,Bronchial Asthma,Asthmas
D016022 Case-Control Studies Comparisons that start with the identification of persons with the disease or outcome of interest and a control (comparison, referent) group without the disease or outcome of interest. The relationship of an attribute is examined by comparing both groups with regard to the frequency or levels of outcome over time. Case-Base Studies,Case-Comparison Studies,Case-Referent Studies,Matched Case-Control Studies,Nested Case-Control Studies,Case Control Studies,Case-Compeer Studies,Case-Referrent Studies,Case Base Studies,Case Comparison Studies,Case Control Study,Case Referent Studies,Case Referrent Studies,Case-Comparison Study,Case-Control Studies, Matched,Case-Control Studies, Nested,Case-Control Study,Case-Control Study, Matched,Case-Control Study, Nested,Case-Referent Study,Case-Referrent Study,Matched Case Control Studies,Matched Case-Control Study,Nested Case Control Studies,Nested Case-Control Study,Studies, Case Control,Studies, Case-Base,Studies, Case-Comparison,Studies, Case-Compeer,Studies, Case-Control,Studies, Case-Referent,Studies, Case-Referrent,Studies, Matched Case-Control,Studies, Nested Case-Control,Study, Case Control,Study, Case-Comparison,Study, Case-Control,Study, Case-Referent,Study, Case-Referrent,Study, Matched Case-Control,Study, Nested Case-Control
D053263 Gene Regulatory Networks Interacting DNA-encoded regulatory subsystems in the GENOME that coordinate input from activator and repressor TRANSCRIPTION FACTORS during development, cell differentiation, or in response to environmental cues. The networks function to ultimately specify expression of particular sets of GENES for specific conditions, times, or locations. Gene Circuits,Gene Modules,Gene Networks,Transcriptional Networks,Gene Module,Circuit, Gene,Circuits, Gene,Gene Circuit,Gene Network,Gene Regulatory Network,Module, Gene,Modules, Gene,Network, Gene,Network, Gene Regulatory,Network, Transcriptional,Networks, Gene,Networks, Gene Regulatory,Networks, Transcriptional,Regulatory Network, Gene,Regulatory Networks, Gene,Transcriptional Network
D060066 Protein Interaction Maps Graphs representing sets of measurable, non-covalent physical contacts with specific PROTEINS in living organisms or in cells. Protein-Protein Interaction Map,Protein-Protein Interaction Network,Protein Interaction Networks,Interaction Map, Protein,Interaction Map, Protein-Protein,Interaction Network, Protein,Interaction Network, Protein-Protein,Map, Protein Interaction,Map, Protein-Protein Interaction,Network, Protein Interaction,Network, Protein-Protein Interaction,Protein Interaction Map,Protein Interaction Network,Protein Protein Interaction Map,Protein Protein Interaction Network,Protein-Protein Interaction Maps,Protein-Protein Interaction Networks
D019175 DNA Methylation Addition of methyl groups to DNA. DNA methyltransferases (DNA methylases) perform this reaction using S-ADENOSYLMETHIONINE as the methyl group donor. DNA Methylations,Methylation, DNA,Methylations, DNA
D020869 Gene Expression Profiling The determination of the pattern of genes expressed at the level of GENETIC TRANSCRIPTION, under specific circumstances or in a specific cell. Gene Expression Analysis,Gene Expression Pattern Analysis,Transcript Expression Analysis,Transcriptome Profiling,Transcriptomics,mRNA Differential Display,Gene Expression Monitoring,Transcriptome Analysis,Analyses, Gene Expression,Analyses, Transcript Expression,Analyses, Transcriptome,Analysis, Gene Expression,Analysis, Transcript Expression,Analysis, Transcriptome,Differential Display, mRNA,Differential Displays, mRNA,Expression Analyses, Gene,Expression Analysis, Gene,Gene Expression Analyses,Gene Expression Monitorings,Gene Expression Profilings,Monitoring, Gene Expression,Monitorings, Gene Expression,Profiling, Gene Expression,Profiling, Transcriptome,Profilings, Gene Expression,Profilings, Transcriptome,Transcript Expression Analyses,Transcriptome Analyses,Transcriptome Profilings,mRNA Differential Displays
D035683 MicroRNAs Small double-stranded, non-protein coding RNAs, 21-25 nucleotides in length generated from single-stranded microRNA gene transcripts by the same RIBONUCLEASE III, Dicer, that produces small interfering RNAs (RNA, SMALL INTERFERING). They become part of the RNA-INDUCED SILENCING COMPLEX and repress the translation (TRANSLATION, GENETIC) of target RNA by binding to homologous 3'UTR region as an imperfect match. The small temporal RNAs (stRNAs), let-7 and lin-4, from C. elegans, are the first 2 miRNAs discovered, and are from a class of miRNAs involved in developmental timing. RNA, Small Temporal,Small Temporal RNA,miRNA,stRNA,Micro RNA,MicroRNA,Primary MicroRNA,Primary miRNA,miRNAs,pre-miRNA,pri-miRNA,MicroRNA, Primary,RNA, Micro,Temporal RNA, Small,miRNA, Primary,pre miRNA,pri miRNA

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