PMID- 26362438
OWN - NLM
STAT- MEDLINE
DCOM- 20160808
LR  - 20220317
IS  - 1942-3268 (Electronic)
IS  - 1942-325X (Print)
IS  - 1942-3268 (Linking)
VI  - 8
IP  - 5
DP  - 2015 Oct
TI  - Molecular Characterization of the NLRC4 Expression in Relation to Interleukin-18 
      Levels.
PG  - 717-26
LID - 10.1161/CIRCGENETICS.115.001079 [doi]
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 x 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.
CI  - (c) 2015 American Heart Association, Inc.
FAU - Zeller, Tanja
AU  - Zeller T
FAU - Haase, Tina
AU  - Haase T
FAU - Muller, Christian
AU  - Muller C
FAU - Riess, Helene
AU  - Riess H
FAU - Lau, Denise
AU  - Lau D
FAU - Zeller, Simon
AU  - Zeller S
FAU - Krause, Jasmin
AU  - Krause J
FAU - Baumert, Jens
AU  - Baumert J
FAU - Pless, Ole
AU  - Pless O
FAU - Dupuis, Josee
AU  - Dupuis J
FAU - Wild, Philipp S
AU  - Wild PS
FAU - Eleftheriadis, Medea
AU  - Eleftheriadis M
FAU - Waldenberger, Melanie
AU  - Waldenberger M
FAU - Zeilinger, Sonja
AU  - Zeilinger S
FAU - Ziegler, Andreas
AU  - Ziegler A
FAU - Peters, Annette
AU  - Peters A
FAU - Tiret, Laurence
AU  - Tiret L
FAU - Proust, Carole
AU  - Proust C
FAU - Marzi, Carola
AU  - Marzi C
FAU - Munzel, Thomas
AU  - Munzel T
FAU - Strauch, Konstantin
AU  - Strauch K
FAU - Prokisch, Holger
AU  - Prokisch H
FAU - Lackner, Karl J
AU  - Lackner KJ
FAU - Herder, Christian
AU  - Herder C
FAU - Thorand, Barbara
AU  - Thorand B
FAU - Benjamin, Emilia J
AU  - Benjamin EJ
FAU - Blankenberg, Stefan
AU  - Blankenberg S
FAU - Koenig, Wolfgang
AU  - Koenig W
FAU - Schnabel, Renate B
AU  - Schnabel RB
LA  - eng
GR  - N02-HL-6-4278/HL/NHLBI NIH HHS/United States
GR  - N01-HC-25195/HC/NHLBI NIH HHS/United States
GR  - R01 HL076784/HL/NHLBI NIH HHS/United States
GR  - AG028321/AG/NIA NIH HHS/United States
GR  - HL064753/HL/NHLBI NIH HHS/United States
GR  - HL076784/HL/NHLBI NIH HHS/United States
GR  - 1S10RR163736-01A1/RR/NCRR NIH HHS/United States
GR  - N01HC25195/HL/NHLBI NIH HHS/United States
GR  - R01 AG028321/AG/NIA NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20150911
PL  - United States
TA  - Circ Cardiovasc Genet
JT  - Circulation. Cardiovascular genetics
JID - 101489144
RN  - 0 (CARD Signaling Adaptor Proteins)
RN  - 0 (Calcium-Binding Proteins)
RN  - 0 (Inflammasomes)
RN  - 0 (Interleukin-18)
RN  - 0 (NLRC4 protein, human)
RN  - 0 (Protein Isoforms)
SB  - IM
MH  - Alleles
MH  - CARD Signaling Adaptor Proteins/*genetics
MH  - Calcium-Binding Proteins/*genetics
MH  - Cohort Studies
MH  - Computer Simulation
MH  - Diabetes Mellitus, Type 2/*genetics/metabolism
MH  - Gene Expression
MH  - Genome-Wide Association Study
MH  - HEK293 Cells
MH  - Humans
MH  - Inflammasomes/metabolism
MH  - Interleukin-18/*metabolism
MH  - Polymorphism, Single Nucleotide
MH  - Protein Isoforms/genetics
PMC - PMC4618032
MID - NIHMS724275
OTO - NOTNLM
OT  - gene expression
OT  - genetic variation
OT  - inflammasomes
OT  - interleukin-18
OT  - transcription factors
COIS- Conflict of Interest Disclosures: None.
EDAT- 2015/09/13 06:00
MHDA- 2016/08/09 06:00
PMCR- 2016/10/01
CRDT- 2015/09/13 06:00
PHST- 2015/03/10 00:00 [received]
PHST- 2015/08/24 00:00 [accepted]
PHST- 2015/09/13 06:00 [entrez]
PHST- 2015/09/13 06:00 [pubmed]
PHST- 2016/08/09 06:00 [medline]
PHST- 2016/10/01 00:00 [pmc-release]
AID - CIRCGENETICS.115.001079 [pii]
AID - 10.1161/CIRCGENETICS.115.001079 [doi]
PST - ppublish
SO  - Circ Cardiovasc Genet. 2015 Oct;8(5):717-26. doi: 
      10.1161/CIRCGENETICS.115.001079. Epub 2015 Sep 11.