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Open Access Green as soon as Postprint is submitted to ZB.
Molecular characterization of the NLRC4 expression in relation to interleukin-18 levels.
Circ. Cardiovasc. Genet. 8, 717-726 (2015)
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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Publication type
Article: Journal article
Document type
Scientific Article
Keywords
Inflammasome ; Interleukin 18 ; Nlrc4 ; Pu.1 ; Gene Expression ; Gene Regulation ; Genetic Variation ; Transcription Factors
ISSN (print) / ISBN
1942-325X
e-ISSN
1942-3268
Quellenangaben
Volume: 8,
Issue: 5,
Pages: 717-726
Publisher
Lippincott Williams & Wilkins
Publishing Place
Hagerstown, Md
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Reviewing status
Peer reviewed