Bioinformatics Analysis of Gene Expression in Peripheral Blood Mononuclear Cells from Children with Type 1 Diabetes in 3 Periods

Abstract

To explore the expression changes of potential key genes and relevant biological processes in peripheral blood mononuclear cells of children with newly diagnosis of type 1 diabetes (T1D).Microarray data GSE9006 were downloaded from Gene Expression Omnibus (GEO) database, including peripheral blood mononuclear cells samples from 43 children with newly diagnosed T1D (NEW), 19 one-month (1-MO) follow-up samples, 19 4-month (4-MO) follow-up samples and 24 healthy controls. The differentially expressed genes (DEGs) were identified using Affy package in R, and cluster analysis of DEGs were performed following functional enrichment analysis with Database for Annotation, Visualization and Integrated Discovery (DAVID) and construction of protein-protein interaction (PPI) network with STRING database.We identified 73, 73, 96 DEGs in NEW group, 1-MO group and 4-MO group, respectively by comparing with healthy controls with |logFC|>0.58 and P-value<0.05. The cluster analysis of these DEGs showed that 4 genes, including human leukocyte antigen (HLA-DQA1), HLA-DRB4, integrin 3 (ITGB3) and killer cell lectin-like receptor subfamily F member 1 (KLRF1) were all significantly expressed in 3 groups, which were significantly enriched in asthma, T1D and intestinal immune network for IgA production pathway. And 57 genes enriched in cluster 5, which were only differentially expressed in NEW group, were involved in response to wounding, inflammatory response and blood coagulation as well as chemokine signaling pathway. Besides, the hub genes in PPI network of cluster 5 were identified, containing FOS, pro-platelet basic protein (PPBP), interleukin 8 (IL8), formyl peptide receptor-like 2 (FPR2) and platelet factor 4 (PF4).HLA-DQA1, HLA-DRB4, ITGB3 and KLRF1 might be targets for treatment of T1D, and 5 hub proteins, FOS, PPBP, IL8, FPR2 and PF4, were likely to be new markers for diagnosis of T1D.

Integrated analysis of different microarray studies to identify candidate genes in type 1 diabetes

“…26 Previous microarray studies showed that KLRF1 and KLRD1, expressed by natural killer (NK) cells, were dysregulated in PBMCs of T1D subjects. 27,28 The high correlation between HLA-DRB4 and T1D has been widely accepted, with HLA-DRB4 essential in self-versus non-self-immune recognition. [29][30][31] Of note, ZBTB16 was identified as a significant hub protein in the key T1D gene network.…”

“…In addition, MAFB is implicated in enterovirus infections through regulation of transcription of type I interferon, predisposing human islet cells to coxsackievirus infection or persistence, thus increasing susceptibility to T1D . Previous microarray studies showed that KLRF1 and KLRD1 , expressed by natural killer (NK) cells, were dysregulated in PBMCs of T1D subjects . The high correlation between HLA‐DRB4 and T1D has been widely accepted, with HLA‐DRB4 essential in self‐ versus non‐self‐immune recognition …”

Quality of Life and Psychological Screening in Children with Type 1 Diabetes and their Mothers

“…Type 1 diabetes mellitus (T1DM) is an important health problem with an increasing incidence worldwide [1,2]. The insulin-producing pancreatic beta cells are destroyed in individuals with T1DM resulting in lifetime dependence of exogenous insulin [2,3]. Type 1 diabetes, as a serious and lifelong disorder leads to a lot of systemic complications [4,5].…”

Differences in gene expression related to the results of obesity treatment, peak oxygen uptake and fatty acid metabolism measured in a cardiopulmonary exercise test

“…Nonetheless, our study gives a unique insight into in vivo gene expression. Based on the data by Liu et al, 44 we can estimate which cell type is responsible for the observed changes in gene expression. Similarly, there are tools for a post hoc extrapolation of mixed -cell population lines in epigenetic studies.…”