{"entity": "publication", "iuid": "26152da2254b44e3a27bbdf965984b5c", "timestamp": "2026-03-16T23:45:23.603Z", "links": {"self": {"href": "https://publications.scilifelab.se/publication/26152da2254b44e3a27bbdf965984b5c.json"}, "display": {"href": "https://publications.scilifelab.se/publication/26152da2254b44e3a27bbdf965984b5c"}}, "title": "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).", "authors": [{"family": "Johansson", "given": "\u00c5sa", "initials": "\u00c5"}, {"family": "Eriksson", "given": "Niclas", "initials": "N"}, {"family": "Becker", "given": "Richard C", "initials": "RC"}, {"family": "Storey", "given": "Robert F", "initials": "RF"}, {"family": "Himmelmann", "given": "Anders", "initials": "A"}, {"family": "Hagstr\u00f6m", "given": "Emil", "initials": "E"}, {"family": "Varenhorst", "given": "Christoph", "initials": "C"}, {"family": "Axelsson", "given": "Tomas", "initials": "T"}, {"family": "Barratt", "given": "Bryan J", "initials": "BJ"}, {"family": "James", "given": "Stefan K", "initials": "SK"}, {"family": "Katus", "given": "Hugo A", "initials": "HA"}, {"family": "Steg", "given": "Philippe Gabriel", "initials": "PG"}, {"family": "Syv\u00e4nen", "given": "Ann-Christine", "initials": "AC", "orcid": "0000-0002-9681-9146", "researcher": {"href": "https://publications.scilifelab.se/researcher/f7012e35025543379380cb90efd71243.json"}}, {"family": "Wallentin", "given": "Lars", "initials": "L"}, {"family": "Siegbahn", "given": "Agneta", "initials": "A"}, {"family": "PLATO Investigators", "given": null, "initials": null}], "type": "journal article", "published": "2015-06-00", "journal": {"volume": "8", "issn": "1942-3268", "issue": "3", "pages": "498-506", "title": "Circ Cardiovasc Genet", "issn-l": null}, "abstract": "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.\n\nBaseline plasma IL-18 levels were measured in 16\u2009633 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<3.15\u00d710(-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=6.99\u00d710(-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.\n\nOur 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.", "doi": "10.1161/CIRCGENETICS.114.000724", "pmid": "25747584", "labels": {"National Genomics Infrastructure": null, "NGI Uppsala (SNP&SEQ Technology Platform)": null}, "xrefs": [{"db": "pii", "key": "CIRCGENETICS.114.000724"}], "notes": [], "created": "2017-05-02T12:57:28.183Z", "modified": "2021-07-07T15:11:02.345Z"}