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Hier finden Sie wissenschaftliche Publikationen aus den Fraunhofer-Instituten. Molecular characterization of the NLRC4 expression in relation to interleukin-18 levels
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Zeller, T.; Haase, T.; Müller, C.; Riess, H.; Lau, D.; Zeller, S.; Krause, J.; Baumert, J.; Pless, O.; Dupuis, J.; Wild, P.S.; Eleftheriadis, M.; Waldenberger, M.; Zeilinger, S.; Ziegler, A.; Peters, A.; Tiret, L.; Proust, C.; Marzi, C.; Munzel, T.; Strauch, K.; Prokisch, H.; Lackner, KJ.; Herder, C.; Thorand, B.; Benjamin, E.J.; Blankenberg, S.; Koenig, W.; Schnabel, R.B. | Circulation. Cardiovascular genetics 8 (2015), No.5, pp.717-726 ISSN: 1942-325X ISSN: 1942-3268 |
| National Institutes of Health NIH HL076784 |
| National Institutes of Health NIH AG028321 |
| National Institutes of Health NIH HL064753 |
| Deutsche Forschungsgemeinschaft DFG SCHN 1149/1-1 |
| Deutsche Forschungsgemeinschaft DFG TH 784/2-1 |
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| English |
| Journal Article |
| Fraunhofer IME () |
Abstract
Background Interleukin-18 (IL-18) is a pleiotropic cytokine centrally involved in the cytokine cascade with complex immunomodulatory functions in innate and acquired immunity. Circulating IL-18 concentrations are associated with type 2 diabetes mellitus, cardiovascular events, and diverse inflammatory and autoimmune disorders. Methods and Results To identify causal variants affecting circulating IL-18 concentrations, we applied various omics and molecular biology approaches. By genome-wide association study, we confirmed association of IL-18 levels with a single nucleotide polymorphism in the untranslated exon 2 of the inflammasome component NLRC4 (NLR family, caspase recruitment domain-containing 4) gene on chromosome 2 (rs385076; P=2.4x10(-45)). Subsequent molecular analyses by gene expression analysis and reporter gene assays indicated an effect of rs385076 on NLRC4 expression and differential isoform usage by modulating binding of the transcription factor PU.1. Conclusions Our study provides evidence for the functional causality of single nucleotide polymorphism rs385076 within the NLRC4 gene in relation to IL-18 activation.