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Transcriptional profiling of type 1 diabetes genes on chromosome 21 in a rat beta-cell line and human pancreatic islets

Bergholdt, R
Karlsen, A E
Hagedorn, P H
Aalund, M
Nielsen, J H
Kruhøffer, M
Orntoft, T
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Published in Genes and Immunity. 2007, vol. 8, no. 3, p. 232-8
Abstract We recently finemapped a type 1 diabetes (T1D)-linked region on chromosome 21, indicating that one or more T1D-linked genes exist in this region with 33 annotated genes. In the current study, we have taken a novel approach using transcriptional profiling in predicting and prioritizing the most likely candidate genes influencing beta-cell function in this region. Two array-based approaches were used, a rat insulinoma cell line (INS-1alphabeta) overexpressing pancreatic duodenum homeobox 1 (pdx-1) and treated with interleukin 1beta (IL-1beta) as well as human pancreatic islets stimulated with a mixture of cytokines. Several candidate genes with likely functional significance in T1D were identified. Genes showing differential expression in the two approaches were highly similar, supporting the role of these specific gene products in cytokine-induced beta-cell damage. These were genes involved in cytokine signaling, oxidative phosphorylation, defense responses and apoptosis. The analyses, furthermore, revealed several transcription factor binding sites shared by the differentially expressed genes and by genes demonstrating highly similar expression profiles with these genes. Comparable findings in the rat beta-cell line and human islets support the validity of the methods used and support this as a valuable approach for gene mapping and identification of genes with potential functional significance in T1D, within a region of linkage.
Keywords AdolescentAdultAnimalsCell Line, TumorChildChromosomes, Human, Pair 21/geneticsDiabetes Mellitus, Type 1/geneticsFemaleGene Expression ProfilingGenetic Predisposition to DiseaseHomeodomain Proteins/geneticsHumansInsulin-Secreting Cells/drug effects/metabolismInsulinoma/geneticsInterleukin-1beta/pharmacologyIslets of Langerhans/drug effects/metabolismMaleMiddle AgedPancreatic Neoplasms/geneticsRatsTrans-Activators/genetics
PMID: 17330137
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BERGHOLDT, R et al. Transcriptional profiling of type 1 diabetes genes on chromosome 21 in a rat beta-cell line and human pancreatic islets. In: Genes and Immunity, 2007, vol. 8, n° 3, p. 232-8. doi: 10.1038/sj.gene.6364379 https://archive-ouverte.unige.ch/unige:33455

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Deposited on : 2014-01-20

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