Dataset Information

Network-Based Association Study of Obesity and Type 2 Diabetes with Gene Expression Profiles.

ABSTRACT: The increased prevalence of obesity and type 2 diabetes (T2D) has become an important factor affecting the health of the human. Obesity is commonly considered as a major risk factor for the development of T2D. However, the molecular mechanisms of the disease relations are not well discovered yet. In this study, the combination of multiple differential expression profiles and a comprehensive biological network of obesity and T2D allowed us to identify and compare the disease-responsive active modules and subclusters. The results demonstrated that the connection between obesity and T2D mainly relied on several pathways involved in the digestive metabolism, immunization, and signal transduction, such as adipocytokine, chemokine signaling pathway, T cell receptor signaling pathway, and MAPK signaling pathways. The relationships of almost all of these pathways with obesity and T2D have been verified by the previous reports individually. We also found that the different parts in the same pathway are activated in obesity and T2D. The association of cancer, obesity, and T2D was identified too here. As a conclusion, our network-based method not only gives better support for the close connection between obesity and T2D, but also provides a systemic view in understanding the molecular functions underneath the links. It should be helpful in the development of new therapies for obesity, T2D, and the associated diseases.

SUBMITTER: Zhang S

PROVIDER: S-EPMC4530213 | biostudies-literature | 2015

REPOSITORIES: biostudies-literature

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Network-Based Association Study of Obesity and Type 2 Diabetes with Gene Expression Profiles.

Zhang Siyi S Wang Bo B Shi Jingsong J Li Jing J

BioMed research international 20150727

The increased prevalence of obesity and type 2 diabetes (T2D) has become an important factor affecting the health of the human. Obesity is commonly considered as a major risk factor for the development of T2D. However, the molecular mechanisms of the disease relations are not well discovered yet. In this study, the combination of multiple differential expression profiles and a comprehensive biological network of obesity and T2D allowed us to identify and compare the disease-responsive active mod ...[more]

PMID: 26273637

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Project description:Type 1 diabetes (T1D) is an autoimmune disease that is typically diagnosed in children. The aim of the present study was to identify potential genes involved in the pathogenesis of childhood T1D. Two datasets of mRNA expression in children with T1D were obtained from the Gene Expression Omnibus (GEO). Differentially expressed genes (DEGs) in children with T1D were identified. Functional analysis was performed and a protein‑protein interaction (PPI) network was constructed, as was a transcription factor (TF)‑target network. The expression of selected DEGs was further assessed using reverse transcription‑quantitative polymerase chain reaction (RT‑qPCR) analysis. Electronic validation and diagnostic value analysis of the identified DEGs [cytokine inducible SH2 containing protein (CISH), SR‑related CTD associated factor 11 (SCAF11), estrogen receptor 1 (ESR1), Rho GTPase activating protein 25 (ARHGAP25), major histocompatibility complex, class II, DR β4 (HLA‑DRB4) and interleukin 23 subunit α (IL23A)] was performed in the GEO dataset. Compared with the normal control group, a total of 1,467 DEGs with P<0.05 were identified in children with T1D. CISH and SCAF11 were determined to be the most up‑ and downregulated genes, respectively. Heterogeneous nuclear ribonucleoprotein D (HNRNPD; degree=33), protein kinase AMP‑activated catalytic subunit α1 (PRKAA1; degree=11), integrin subunit α4 (ITGA4; degree=8) and ESR1 (degree=8) were identified in the PPI network as high‑degree genes. ARHGAP25 (degree=12), HNRNPD (degree=10), HLA‑DRB4 (degree=10) and IL23A (degree=9) were high‑degree genes identified in the TF‑target network. RT‑qPCR revealed that the expression of HNRNPD, PRKAA1, ITGA4 and transporter 2, ATP binding cassette subfamily B member was consistent with the results of the integrated analysis. Furthermore, the results of the electronic validation were consistent with the bioinformatics analysis. SCAF11, CISH and ARHGAP25 were identified to possess value as potential diagnostic markers for children with T1D. In conclusion, identifying DEGs in children with T1D may contribute to our understanding of its pathogenesis, and such DEGs may be used as diagnostic biomarkers for children with T1D.

Project description:The HSD11B1 gene is highly expressed in abdominal adipose tissue, and the enzyme it encodes catalyzes the interconversion of inactive cortisone to hormonally active cortisol. Genetic abnormalities of HSD11B1 have been associated with the development of abnormal glucose metabolism and body fat distribution. To systematically review studies evaluating the association of HSD11B1 gene expression in abdominal adipose tissue and HSD11B1 polymorphisms with obesity, the metabolic syndrome (MetS), and type 2 diabetes (T2DM), we conducted a search in MEDLINE, SCOPUS, and Cochrane Library databases in April 2015. The inclusion criteria were observational studies (cross-sectional, cohort, or case-control), conducted in adults, which analyzed the relationship of HSD11B1 polymorphisms and/or HSD11B1 expression in abdominal adipose tissue with obesity, MetS, or T2DM. Of 802 studies retrieved, 32 met the inclusion criteria (23 gene expression and 9 polymorphism studies). Twenty one studies analyzed the relationship between abdominal subcutaneous and/or visceral HSD11B1 expression with central and/or generalized obesity. Most studies reported that abdominal adipose HSD11B1 expression increased with increasing body mass index (15 studies) and abnormalities of glucose metabolism (7 studies), and varied with the presence of MetS (3 studies). Nine studies analyzed the association of 26 different HSD11B1 polymorphic variants with obesity, MetS, and T2DM. Only an Indian study found an association between a polymorphic variant at the HSD11B1 gene with MetS whereas in Pima Indians another polymorphic variant was found to be associated with T2DM. While the literature suggests that HSD11B1 is hyperexpressed in abdominal adipose tissue in subjects with obesity and abnormal glucose metabolism, this seems to be not true for HSD11B1 gene expression and MetS. Although an association of polymorphic variants of HSD11B1 with MetS in Indians and in the T2DM population of Pima Indians were found, most studies did not find a relationship between genetic polymorphic variants of HSD11B1 and obesity, MetS, and T2DM. Their reported conflicting and inconclusive results, suggesting that polymorphic variants of HSD11B1 may have only a small role in the development of metabolic abnormalities of susceptible populations in the development of MetS and T2DM.

Dataset Information

Network-Based Association Study of Obesity and Type 2 Diabetes with Gene Expression Profiles.

Publications

Network-Based Association Study of Obesity and Type 2 Diabetes with Gene Expression Profiles.

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