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NLRC4 Inflammasome ...
NLRC4 Inflammasome Is an Important Regulator of Interleukin-18 Levels in Patients With Acute Coronary Syndromes Genome-Wide Association Study in the PLATelet inhibition and patient Outcomes Trial (PLATO)
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- Johansson, Åsa (author)
- Uppsala universitet,Medicinsk genetik och genomik,Uppsala kliniska forskningscentrum (UCR)
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- Eriksson, Niclas (author)
- Uppsala universitet,Uppsala kliniska forskningscentrum (UCR)
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Becker, Richard C. (author)
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Storey, Robert F. (author)
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Himmelmann, Anders (author)
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- Hagström, Emil (author)
- Uppsala universitet,Kardiologi
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- Varenhorst, Christoph (author)
- Uppsala universitet,Uppsala kliniska forskningscentrum (UCR),Kardiologi
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- Axelsson, Tomas (author)
- Uppsala universitet,Science for Life Laboratory, SciLifeLab,Molekylär medicin
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Barratt, Bryan J. (author)
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- James, Stefan K. (author)
- Uppsala universitet,Kardiologi,Uppsala kliniska forskningscentrum (UCR)
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Katus, Hugo A. (author)
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Steg, Philippe Gabriel (author)
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- Syvänen, Ann-Christine (author)
- Uppsala universitet,Molekylär medicin,Science for Life Laboratory, SciLifeLab
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- Wallentin, Lars (author)
- Uppsala universitet,Uppsala kliniska forskningscentrum (UCR),Kardiologi
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- Siegbahn, Agneta (author)
- Uppsala universitet,Uppsala kliniska forskningscentrum (UCR),Koagulation och inflammationsvetenskap
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(creator_code:org_t)
- 2015
- 2015
- English.
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In: Circulation. - 1942-325X .- 1942-3268. ; 8:3, s. 498-506
- Related links:
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https://urn.kb.se/re...
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https://doi.org/10.1...
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Abstract
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- Background Interleukin 18 (IL-18) promotes atherosclerotic plaque formation and is increased in patients with acute coronary syndromes. However the relative contribution of genetic variants to the IL-18 levels has not been fully determined. Methods and Results Baseline plasma IL-18 levels were measured in 16633 patients with acute coronary syndrome, of whom 9340 had genetic data that passed genotype quality control. A 2-stage genome-wide association study was performed, followed by combined analyses using >10 million genotyped or imputed genetic markers. Single nucleotide polymorphisms at 3 loci (IL18, NLRC4, and MROH6) were identified (P<3.15x10(-8)) in the discovery cohort (n=3777) and replicated in the remaining patients (n=5563). In the pooled data (discovery+replication cohort), 7 independent associations, in 5 chromosomal regions, were associated with IL-18 levels (minimum P=6.99x10(-72)). Six single nucleotide polymorphisms are located in predicted promoter regions of which one disrupts a transcription factor binding site. One single nucleotide polymorphism in NLRC4 is a rare missense variant, predicted to be deleterious to the protein. Altogether, the identified genetic variants explained 8% of the total variation in IL-18 levels in the cohort. Conclusions Our results show that genetic variants play an important role in determining IL-18 levels in patients with acute coronary syndrome and we have identified genetic variants located in the IL-18 gene (IL18) or close to genes that are involved in procaspase-1 activation (NLRC4 and CARD16, CARD17, and CARD18). These associations also highlight the importance of the NLRC4 inflammasome for IL-18 production in acute coronary syndrome patients.
Subject headings
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Kardiologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Cardiac and Cardiovascular Systems (hsv//eng)
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Medicinsk genetik (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Medical Genetics (hsv//eng)
Keyword
- acute coronary syndrome
- genome-wide association study
- interleukins
Publication and Content Type
- ref (subject category)
- art (subject category)
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- By the author/editor
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Johansson, Åsa
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Eriksson, Niclas
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Becker, Richard ...
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Storey, Robert F ...
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Himmelmann, Ande ...
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Hagström, Emil
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Varenhorst, Chri ...
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Axelsson, Tomas
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Barratt, Bryan J ...
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James, Stefan K.
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Katus, Hugo A.
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Steg, Philippe G ...
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Syvänen, Ann-Chr ...
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Wallentin, Lars
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Siegbahn, Agneta
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- About the subject
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- MEDICAL AND HEALTH SCIENCES
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MEDICAL AND HEAL ...
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and Clinical Medicin ...
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and Cardiac and Card ...
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- MEDICAL AND HEALTH SCIENCES
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MEDICAL AND HEAL ...
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and Basic Medicine
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and Medical Genetics
- Articles in the publication
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Circulation
- By the university
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Uppsala University