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

Integrative analysis of the transcriptome profiles observed in type 1, type 2 and gestational diabetes mellitus reveals the role of inflammation.
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DOI:
10.1186/1755-8794-7-28
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发表时间:
2014-05-23
影响因子:
2.7
通讯作者:
Donadi EA
Donadi EA
中科院分区:
医学3区
文献类型:
--
作者:
Evangelista AF;Collares CV;Xavier DJ;Macedo C;Manoel-Caetano FS;Rassi DM;Foss-Freitas MC;Foss MC;Sakamoto-Hojo ET;Nguyen C;Puthier D;Passos GA;Donadi EA

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1型糖尿病(T1D)是一种自身免疫性疾病,而2型(T2D)和妊娠期糖尿病(GDM)被认为是代谢紊乱。在先前一项评估T1D、T2D和GDM患者外周血单个核细胞转录谱的研究中,我们发现T1D患者的基因谱更接近GDM。为了了解人口学、临床、实验室、病因学和治疗特征对糖尿病转录谱的影响,我们进行了一项分析,将这些特征与数据库中包含的注释基因的基因表达谱整合在一起,数据库中包含关于GWA和免疫细胞表达特征的信息。来自56例患者(19例T1D,20例T2D,17例GDM)的样本与全基因组单色Agilent 4x44k芯片杂交。用分块法筛选非信息性基因,用秩积分析得到差异表达基因。使用David数据库进行功能分析,并使用Genomica工具构建模块图。功能分析能够根据参与炎症的基因区分T1D和GDM患者。差异表达基因的模块图谱显示:i)显示了巨噬细胞和树突状细胞的典型转录图谱;ii)先前通过关联和荟萃分析研究发现与糖尿病并发症有关,iii)受病程、肥胖、妊娠次数、血糖水平和药物使用(如二甲双胍)的影响。这是第一个显示流行病学、临床、实验室、免疫致病和治疗特征对T1D、T2D和GDM患者转录谱影响的模块图谱研究。
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. 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. 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. 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.
糖尿病的医疗标准 - 2010年。
DOI: 10.2337/dc10-s011
发表时间: 2010-01
期刊: Diabetes care
影响因子: 16.2
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American Diabetes Association
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发表时间: 2009-01-01
影响因子: 5.8
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发表时间: 2005-09-01
期刊: DIABETES
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