title: Integrative analysis of the transcriptome profiles observed in type 1, type 2 and gestational diabetes mellitus reveals the role of inflammation.
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.
  
  
  CONCLUSIONS
  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.
authors.forename: Adriane F
authors.initials: AF
authors.lastname: Evangelista
authors.forename: Cristhianna V A
authors.initials: CV
authors.lastname: Collares
authors.forename: Danilo J
authors.initials: DJ
authors.lastname: Xavier
authors.forename: Claudia
authors.initials: C
authors.lastname: Macedo
authors.forename: Fernanda S
authors.initials: FS
authors.lastname: Manoel-Caetano
authors.forename: Diane M
authors.initials: DM
authors.lastname: Rassi
authors.forename: Maria C
authors.initials: MC
authors.lastname: Foss-Freitas
authors.forename: Milton C
authors.initials: MC
authors.lastname: Foss
authors.forename: Elza T
authors.initials: ET
authors.lastname: Sakamoto-Hojo
authors.forename: Catherine
authors.initials: C
authors.lastname: Nguyen
authors.forename: Denis
authors.initials: D
authors.lastname: Puthier
authors.forename: Geraldo A
authors.initials: GA
authors.lastname: Passos
authors.affiliation: Molecular Immunogenetics Group, Department of Genetics, Faculty of Medicine of Ribeirão Preto, University of São Paulo (USP), 14049-900 Ribeirão Preto, SP, Brazil. eadonadi@fmrp.usp.br.
authors.forename: Eduardo A
authors.initials: EA
authors.lastname: Donadi
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000465:Algorithms; D016000:Cluster Analysis; D003710:Demography; D003922:Diabetes Mellitus, Type 1 / Q000235:genetics* / Q000473:pathology; D003924:Diabetes Mellitus, Type 2 / Q000235:genetics* / Q000473:pathology; D016640:Diabetes, Gestational / Q000235:genetics* / Q000473:pathology; D005260:Female; D020869:Gene Expression Profiling; D006801:Humans; D007249:Inflammation / Q000235:genetics*; D008297:Male; D008390:Markov Chains; D008875:Middle Aged; D020411:Oligonucleotide Array Sequence Analysis; D011247:Pregnancy; D025341:Principal Component Analysis; D060888:Real-Time Polymerase Chain Reaction; D015203:Reproducibility of Results; D020133:Reverse Transcriptase Polymerase Chain Reaction; D059467:Transcriptome / Q000235:genetics*; D055815:Young Adult