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Tiret, Laurence; Godefroy, Tiphaine; Lubos, Edith; Nicaud, Viviane; Tregouet, David-Alexandre; Barbaux, Sandrine; Schnabel, Renate; Bickel, Christoph; Espinola-Klein, Christine; Poirier, Odette; Perret, Claire; Münzel, Thomas; Rupprecht, Hans-Jurgen; Lackner, Karl; Cambien, François; Blankenberg, Stefan

Genetic Analysis of the Interleukin-18 System Highlights the Role of the Interleukin-18 Gene in Cardiovascular Disease

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  • Medientyp: E-Artikel
  • Titel: Genetic Analysis of the Interleukin-18 System Highlights the Role of the Interleukin-18 Gene in Cardiovascular Disease
  • Beteiligte: Tiret, Laurence; Godefroy, Tiphaine; Lubos, Edith; Nicaud, Viviane; Tregouet, David-Alexandre; Barbaux, Sandrine; Schnabel, Renate; Bickel, Christoph; Espinola-Klein, Christine; Poirier, Odette; Perret, Claire; Münzel, Thomas; Rupprecht, Hans-Jurgen; Lackner, Karl; Cambien, François; Blankenberg, Stefan
  • Erschienen: Ovid Technologies (Wolters Kluwer Health), 2005
  • Erschienen in: Circulation
  • Sprache: Englisch
  • DOI: 10.1161/circulationaha.104.519702
  • ISSN: 1524-4539; 0009-7322
  • Schlagwörter: Physiology (medical) ; Cardiology and Cardiovascular Medicine
  • Entstehung:
  • Anmerkungen:
  • Beschreibung: <jats:p> <jats:bold> <jats:italic>Background—</jats:italic> </jats:bold> Interleukin (IL)-18 plays a key role in atherosclerosis and its complications. The present study investigated the genetic variability of 4 genes of the IL-18 system— <jats:italic>IL18</jats:italic> , <jats:italic>IL18R1</jats:italic> , <jats:italic>IL18RAP</jats:italic> , and <jats:italic>IL18BP</jats:italic> —in relation to circulating IL-18 levels and cardiovascular mortality. </jats:p> <jats:p> <jats:bold> <jats:italic>Methods and Results—</jats:italic> </jats:bold> Twenty-two polymorphisms were genotyped in 1288 patients with coronary artery disease prospectively followed up during a median period of 5.9 years. The end point was death from cardiovascular causes (n=142). Baseline IL-18 levels were predictive of cardiovascular deaths occurring during ≤4 years of follow-up (HR=2.96, 95% CI 1.54 to 5.70, <jats:italic>P</jats:italic> =0.001 for the top compared with the bottom quartile) but not of later deaths. Haplotypes of the <jats:italic>IL18</jats:italic> gene were associated with IL-18 levels ( <jats:italic>P</jats:italic> =0.002) and cardiovascular mortality ( <jats:italic>P</jats:italic> =0.006) after adjustment for cardiovascular risk factors. The same haplotype was associated with both a 9% lowering effect on IL-18 levels and a protective effect on risk (HR=0.57, 95% CI 0.36 to 0.92). <jats:italic>IL18</jats:italic> haplotypes explained only 2% of IL-18 variability. Adjustment for baseline IL-18 levels abolished the association of haplotypes with cardiovascular risk. The haplotype associated with phenotypes was the only one carrying the minor allele of the <jats:italic>IL18</jats:italic> /A+183G polymorphism located in the 3′untranslated region and potentially affecting mRNA stability. The other genes of the system were not related to IL-18 levels or cardiovascular outcome. </jats:p> <jats:p> <jats:bold> <jats:italic>Conclusion—</jats:italic> </jats:bold> Variations of the <jats:italic>IL18</jats:italic> gene consistently influence circulating levels of IL-18 and clinical outcome in patients with coronary artery disease, which supports the hypothesis of a causal role of IL-18 in atherosclerosis and its complications. </jats:p>
  • Zugangsstatus: Freier Zugang