Expression features of genetic landscape which predispose an individual to the type 1 diabetes are poorly understood. We addressed this question by comparing gene expression profile of freshly isolated peripheral blood mononuclear cells isolated from either patients with type 1 diabetes (T1D), or their first-degree relatives or healthy controls. Our aim was to establish whether a distinct type of 'prodiabetogenic' gene expression pattern in the group of relatives of patients with T1D could be identified. Whole-genome expression profile of nine patients with T1D, their ten first-degree relatives and ten healthy controls was analysed using the human high-density expression microarray chip. Functional aspects of candidate genes were assessed using the MetaCore software. The highest number of differentially expressed genes (547) was found between the autoantibody-negative healthy relatives and the healthy controls. Some of them represent genes critically involved in the regulation of innate immune responses such as TLR signalling and CCR3 signalling in eosinophiles, humoral immune reactions such as BCR pathway, costimulation and cytokine responses mediated by CD137, CD40 and CD28 signalling and IL-1 proinflammatory pathway. Our data demonstrate that expression profile of healthy relatives of patients with T1D is clearly distinct from the pattern found in the healthy controls. That especially concerns differential activation status of genes and signalling pathways involved in proinflammatory processes and those of innate immunity and humoral reactivity. Thus, we posit that the study of the healthy relative's gene expression pattern is instrumental for the identification of novel markers associated with the development of diabetes.
- MeSH
- anotace sekvence MeSH
- autoimunita MeSH
- autoprotilátky biosyntéza genetika MeSH
- CD antigeny genetika imunologie MeSH
- celogenomová asociační studie MeSH
- diabetes mellitus 1. typu genetika imunologie patologie MeSH
- dítě MeSH
- dospělí MeSH
- humorální imunita MeSH
- interleukin-1 genetika imunologie MeSH
- kojenec MeSH
- leukocyty mononukleární imunologie metabolismus patologie MeSH
- lidé MeSH
- mladiství MeSH
- předškolní dítě MeSH
- primární buněčná kultura MeSH
- přirozená imunita MeSH
- receptory CCR3 genetika imunologie MeSH
- regulace genové exprese imunologie MeSH
- rodina MeSH
- signální transdukce MeSH
- stanovení celkové genové exprese MeSH
- studie případů a kontrol MeSH
- toll-like receptory genetika imunologie MeSH
- Check Tag
- dítě MeSH
- dospělí MeSH
- kojenec MeSH
- lidé MeSH
- mladiství MeSH
- mužské pohlaví MeSH
- předškolní dítě MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
