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Publication Details
AFRICAN RESEARCH NEXUS
SHINING A SPOTLIGHT ON AFRICAN RESEARCH
Molecular Characterization of the NLRC4 Expression in Relation to Interleukin-18 Levels
Circulation: Cardiovascular Genetics, Volume 8, No. 5, Year 2015
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Description
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=2.4×10-45). 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 single nucleotide polymorphism rs385076 within the NLRC4 gene in relation to IL-18 activation. © 2015 American Heart Association, Inc.
Authors & Co-Authors
Zeller, Tanja
Germany, Hamburg
Universitäre Herz- Und Gefäßzentrum Uke Hamburg Gmbh
Germany, Berlin
Deutsches Zentrum Für Herz-kreislauf-forschung E. V.
Germany, Munich
Ludwig-maximilians-universität München
Müller, Christian
Germany, Hamburg
Universitäre Herz- Und Gefäßzentrum Uke Hamburg Gmbh
Germany, Berlin
Deutsches Zentrum Für Herz-kreislauf-forschung E. V.
Riess, Helene
Germany, Oberschleissheim
Institute of Epidemiology Ii
Germany, Ulm
Universitätsklinikum Ulm
Baumert, Jens J.
Germany, Oberschleissheim
Institute of Epidemiology Ii
Dupuis, Josèe
United States, Boston
Boston University
Wild, Philipp S.
France, Paris
Ican Institute for Cardiometabolism and Nutrition
Waldenberger, Melanie
Germany, Oberschleissheim
Institute of Epidemiology Ii
Germany, Oberschleissheim
Research Unit of Molecular Epidemiology
Germany, Berlin
Deutsches Zentrum Für Herz-kreislauf-forschung E. V.
Ziegler, Andreas E.
United States, Boston
Boston University
Peters, Annette Michael
Germany, Oberschleissheim
Institute of Epidemiology Ii
Proust, Carole
Unknown Affiliation
Marzi, Carola S.
Germany, Oberschleissheim
Institute of Epidemiology Ii
Germany, Oberschleissheim
Research Unit of Molecular Epidemiology
Münzel, Tomas F.
Germany, Mainz
Universitätsmedizin Mainz
Strauch, Konstantin
Germany, Freiburg Im Breisgau
Institute of Genetic Epidemiology
Prokisch, Holger
Germany, Oberschleissheim
Helmholtz Center Munich German Research Center for Environmental Health
Germany, Munich
Technische Universität München
Lackner, Karl Johannes
Germany, Berlin
Deutsches Zentrum Für Herz-kreislauf-forschung E. V.
Germany, Dusseldorf
Deutsches Diabetes-zentrum
Herder, Christian
Germany, Lubeck
Universitätsklinikum Schleswig-holstein Campus Lübeck
Germany, Dusseldorf
Deutsches Diabetes-zentrum
Thorand, Barbara
Germany, Oberschleissheim
Institute of Epidemiology Ii
Benjamin, Emelia J.
Germany, Lubeck
Universität zu Lübeck
Blankenberg, Stefan S.
Germany, Hamburg
Universitäre Herz- Und Gefäßzentrum Uke Hamburg Gmbh
Germany, Berlin
Deutsches Zentrum Für Herz-kreislauf-forschung E. V.
Koenig, Wolfgang F.
France, Paris
Sorbonne Université
Schnabel, Renate B.
Germany, Hamburg
Universitäre Herz- Und Gefäßzentrum Uke Hamburg Gmbh
Germany, Berlin
Deutsches Zentrum Für Herz-kreislauf-forschung E. V.
Statistics
Citations: 19
Authors: 21
Affiliations: 19
Identifiers
Doi:
10.1161/CIRCGENETICS.115.001079
ISSN:
1942325X
Research Areas
Genetics And Genomics
Noncommunicable Diseases