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Zeller, T.* ; Haase, T.* ; Müller, C.* ; Riess, H. ; Lau, D.* ; Zeller, S.* ; Krause, J.* ; Baumert, J.J. ; Pless, O.* ; Dupuis, J.* ; Wild, P.S.* ; Eleftheriadis, M.S.* ; Waldenberger, M. ; Zeilinger, S. ; Ziegler, A.* ; Peters, A. ; Tiret, L.* ; Proust, C.* ; Marzi, C. ; Münzel, T.* ; Strauch, K. ; Prokisch, H. ; Lackner, K.J.* ; Herder, C.* ; Thorand, B. ; Benjamin, E.J.* ; Blankenberg, S.* ; Koenig, W.* ; Schnabel, R.B.*

Molecular characterization of the NLRC4 expression in relation to interleukin-18 levels.

Circ. Cardiovasc. Genet. 8, 717-726 (2015)
Verlagsversion DOI
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Open Access Green möglich sobald Postprint bei der ZB eingereicht worden ist.
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, 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 GWAS, we confirmed association of IL-18 levels with a SNP in the untranslated exon 2 of the inflammasome component NLRC4 (NLR family, CARD domain containing 4) gene on chromosome 2 (rs385076, P=2.4×10(-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 SNP rs385076 within the NLRC4 gene in relation to IL-18 activation.
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Publikationstyp Artikel: Journalartikel
Dokumenttyp Wissenschaftlicher Artikel
Schlagwörter Inflammasome ; Interleukin 18 ; Nlrc4 ; Pu.1 ; Gene Expression ; Gene Regulation ; Genetic Variation ; Transcription Factors
ISSN (print) / ISBN 1942-325X
e-ISSN 1942-3268
Quellenangaben Band: 8, Heft: 5, Seiten: 717-726 Artikelnummer: , Supplement: ,
Verlag Lippincott Williams & Wilkins
Verlagsort Hagerstown, Md
Begutachtungsstatus Peer reviewed