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

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    R. Bergholdt, Steno Diabetes Center, Gentofte, Denmark., DenmarkA.E. Karlsen, Steno Diabetes Center, Gentofte, Denmark, Institute for Clinical Science, University of Lund, Lund, Sweden, DenmarkP.H. Hagedorn, Biosystems Department, Risø National Laboratory, Technical University of Denmark, Roskilde, Denmark, DenmarkM. Aalund, Neurotech A/S, Copenhagen, Denmark, DenmarkJ.H. Nielsen, Department of Medical Biochemistry and Genetics, University of Copenhagen, Copenhagen, Denmark, DenmarkMogens Kruhøffer, DenmarkH. Wang, Department of Cell Physiology and Metabolism, University Medical Center, Geneva, Switzerland, SwitzerlandC.B. Wollheim, 7Department of Cell Physiology and Metabolism, University Medical Center, Geneva, Switzerland, SwitzerlandJ. Nerup, Steno Diabetes Center, Gentofte, Denmark, Institute for Clinical Science, University of Lund, Lund, Sweden, DenmarkF. Pociot, Steno Diabetes Center, Gentofte, Denmark, Institute for Clinical Science, University of Lund, Lund, Sweden, Denmark
  • Department of clinical biochemistry
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.
Udgivelsesdato: April
Original languageEnglish
JournalGenes and Immunity
Volume8
Issue number3
Pages (from-to)232-238
Number of pages9
ISSN1466-4879
DOIs
StatePublished - 2007

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