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Molecular Characterization of the NLRC4 Expression in Relation to Interleukin-18 Levels

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Molecular Characterization of the NLRC4 Expression in Relation to Interleukin-18 Levels. / Zeller, Tanja; Haase, Tina; Müller, Christian; Riess, Helene; Lau, Denise; Zeller, Simon; Krause, Jasmin; Baumert, Jens; Pless, Ole; Dupuis, Josée; Wild, Philipp S; Eleftheriadis, Medea; Waldenberger, Melanie; Zeilinger, Sonja; Ziegler, Andreas; Peters, Annette; Tiret, Laurence; Proust, Carole; Marzi, Carola; Munzel, Thomas; Strauch, Konstantin; Prokisch, Holger; Lackner, Karl J; Herder, Christian; Thorand, Barbara; Benjamin, Emilia J; Blankenberg, Stefan; Koenig, Wolfgang; Schnabel, Renate B.

In: CIRC-CARDIOVASC GENE, Vol. 8, No. 5, 10.2015, p. 717-726.

Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review

Harvard

Zeller, T, Haase, T, Müller, C, Riess, H, Lau, D, Zeller, S, Krause, J, Baumert, J, Pless, O, Dupuis, J, Wild, PS, 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, EJ, Blankenberg, S, Koenig, W & Schnabel, RB 2015, 'Molecular Characterization of the NLRC4 Expression in Relation to Interleukin-18 Levels', CIRC-CARDIOVASC GENE, vol. 8, no. 5, pp. 717-726. https://doi.org/10.1161/CIRCGENETICS.115.001079

APA

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., ... Schnabel, R. B. (2015). Molecular Characterization of the NLRC4 Expression in Relation to Interleukin-18 Levels. CIRC-CARDIOVASC GENE, 8(5), 717-726. https://doi.org/10.1161/CIRCGENETICS.115.001079

Vancouver

Zeller T, Haase T, Müller C, Riess H, Lau D, Zeller S et al. Molecular Characterization of the NLRC4 Expression in Relation to Interleukin-18 Levels. CIRC-CARDIOVASC GENE. 2015 Oct;8(5):717-726. https://doi.org/10.1161/CIRCGENETICS.115.001079

Bibtex

@article{c580b29498c14ca8bf8b33828eb3522e,
title = "Molecular Characterization of the NLRC4 Expression in Relation to Interleukin-18 Levels",
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=2.4 × 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.",
keywords = "Alleles, CARD Signaling Adaptor Proteins/genetics, Calcium-Binding Proteins/genetics, Cohort Studies, Computer Simulation, Diabetes Mellitus, Type 2/genetics, Gene Expression, Genome-Wide Association Study, HEK293 Cells, Humans, Inflammasomes/metabolism, Interleukin-18/metabolism, Polymorphism, Single Nucleotide, Protein Isoforms/genetics",
author = "Tanja Zeller and Tina Haase and Christian M{\"u}ller and Helene Riess and Denise Lau and Simon Zeller and Jasmin Krause and Jens Baumert and Ole Pless and Jos{\'e}e Dupuis and Wild, {Philipp S} and Medea Eleftheriadis and Melanie Waldenberger and Sonja Zeilinger and Andreas Ziegler and Annette Peters and Laurence Tiret and Carole Proust and Carola Marzi and Thomas Munzel and Konstantin Strauch and Holger Prokisch and Lackner, {Karl J} and Christian Herder and Barbara Thorand and Benjamin, {Emilia J} and Stefan Blankenberg and Wolfgang Koenig and Schnabel, {Renate B}",
note = "{\textcopyright} 2015 American Heart Association, Inc.",
year = "2015",
month = oct,
doi = "10.1161/CIRCGENETICS.115.001079",
language = "English",
volume = "8",
pages = "717--726",
journal = "CIRC-CARDIOVASC GENE",
issn = "1942-325X",
publisher = "Lippincott Williams and Wilkins",
number = "5",

}

RIS

TY - JOUR

T1 - Molecular Characterization of the NLRC4 Expression in Relation to Interleukin-18 Levels

AU - Zeller, Tanja

AU - Haase, Tina

AU - Müller, Christian

AU - Riess, Helene

AU - Lau, Denise

AU - Zeller, Simon

AU - Krause, Jasmin

AU - Baumert, Jens

AU - Pless, Ole

AU - Dupuis, Josée

AU - Wild, Philipp S

AU - Eleftheriadis, Medea

AU - Waldenberger, Melanie

AU - Zeilinger, Sonja

AU - Ziegler, Andreas

AU - Peters, Annette

AU - Tiret, Laurence

AU - Proust, Carole

AU - Marzi, Carola

AU - Munzel, Thomas

AU - Strauch, Konstantin

AU - Prokisch, Holger

AU - Lackner, Karl J

AU - Herder, Christian

AU - Thorand, Barbara

AU - Benjamin, Emilia J

AU - Blankenberg, Stefan

AU - Koenig, Wolfgang

AU - Schnabel, Renate B

N1 - © 2015 American Heart Association, Inc.

PY - 2015/10

Y1 - 2015/10

N2 - 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.

AB - 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.

KW - Alleles

KW - CARD Signaling Adaptor Proteins/genetics

KW - Calcium-Binding Proteins/genetics

KW - Cohort Studies

KW - Computer Simulation

KW - Diabetes Mellitus, Type 2/genetics

KW - Gene Expression

KW - Genome-Wide Association Study

KW - HEK293 Cells

KW - Humans

KW - Inflammasomes/metabolism

KW - Interleukin-18/metabolism

KW - Polymorphism, Single Nucleotide

KW - Protein Isoforms/genetics

U2 - 10.1161/CIRCGENETICS.115.001079

DO - 10.1161/CIRCGENETICS.115.001079

M3 - SCORING: Journal article

C2 - 26362438

VL - 8

SP - 717

EP - 726

JO - CIRC-CARDIOVASC GENE

JF - CIRC-CARDIOVASC GENE

SN - 1942-325X

IS - 5

ER -