Integrative analysis of the transcriptome profiles observed in type 1, type 2 and gestational diabetes mellitus reveals the role of inflammation

Author(s):Show less -

Evangelista, Adriane F. ^[1] ; Collares, Cristhianna V. A. ^{[1, 2]} ; Xavier, Danilo J. ^[1] ; Macedo, Claudia ^[1] ; Manoel-Caetano, Fernanda S. ^[1] ; Rassi, Diane M. ^[1] ; Foss-Freitas, Maria C. ^[2] ; Foss, Milton C. ^[2] ; Sakamoto-Hojo, Elza T. ^{[1, 3]} ; Nguyen, Catherine ^[4] ; Puthier, Denis ^[4] ; Passos, Geraldo A. ^{[1, 5, 6]} ; Donadi, Eduardo A. ^{[1, 2]}

Affiliation

^[1] Univ Sao Paulo, Mol Immunogenet Grp, Dept Genet, Fac Med Ribeirao Preto, BR-14049900 Ribeirao Preto, SP - Brazil

^[2] Univ Sao Paulo, Div Clin Immunol, Fac Med Ribeirao Preto, BR-14049900 Ribeirao Preto, SP - Brazil

^[3] Univ Sao Paulo, Fac Philosophy Sci & Letters, Dept Biol, BR-14040900 Ribeirao Preto, SP - Brazil

^[4] Aix Marseille Univ, IFR137, INSERM U1090, TAGC, F-13100 Marseille - France

^[5] Univ Sao Paulo, Sch Dent Ribeirao Preto, Dept Morphol Physiol & Basic Pathol, Discipline Genet, BR-14040904 Ribeirao Preto, SP - Brazil

^[6] Univ Sao Paulo, Sch Dent Ribeirao Preto, Dept Morphol Physiol & Basic Pathol, Discipline Mol Biol, BR-14040904 Ribeirao Preto, SP - Brazil

• Document type: Journal article
• Source: BMC MEDICAL GENOMICS; v. 7, MAY 23 2014.
• Web of Science Citations: 16

Abstract

Background: Type 1 diabetes (T1D) is an autoimmune disease, while type 2 (T2D) and gestational diabetes (GDM) are considered metabolic disturbances. In a previous study evaluating the transcript profiling of peripheral mononuclear blood cells obtained from T1D, T2D and GDM patients we showed that the gene profile of T1D patients was closer to GDM than to T2D. To understand the influence of demographical, clinical, laboratory, pathogenetic and treatment features on the diabetes transcript profiling, we performed an analysis integrating these features with the gene expression profiles of the annotated genes included in databases containing information regarding GWAS and immune cell expression signatures. Methods: Samples from 56 (19 T1D, 20 T2D, and 17 GDM) patients were hybridized to whole genome one-color Agilent 4x44k microarrays. Non-informative genes were filtered by partitioning, and differentially expressed genes were obtained by rank product analysis. Functional analyses were carried out using the DAVID database, and module maps were constructed using the Genomica tool. Results: The functional analyses were able to discriminate between T1D and GDM patients based on genes involved in inflammation. Module maps of differentially expressed genes revealed that modulated genes: i) exhibited transcription profiles typical of macrophage and dendritic cells; ii) had been previously associated with diabetic complications by association and by meta-analysis studies, and iii) were influenced by disease duration, obesity, number of gestations, glucose serum levels and the use of medications, such as metformin. Conclusion: This is the first module map study to show the influence of epidemiological, clinical, laboratory, immunopathogenic and treatment features on the transcription profiles of T1D, T2D and GDM patients. (AU)

• FAPESP's process: 10/12069-7 - Gene expression profiles and possible interactions between microRNAs and mRNAs in type 1 Diabetes Mellitus, focusing on response to oxidative stress and DNA repair
• Grantee: Paula Takahashi
• Support Opportunities: Scholarships in Brazil - Doctorate
• FAPESP's process: 08/56594-8 - Control of the transcriptome in diabetes mellitus
• Grantee: Geraldo Aleixo da Silva Passos Júnior
• Support Opportunities: Research Projects - Thematic Grants