title: Glycoprotein 130 polymorphism predicts soluble glycoprotein 130 levels.
abstract: OBJECTIVE
  Interleukin-6 (IL-6) is a key cytokine in inflammatory diseases. It exerts its biological function via binding to a homodimer of its signal transducer glycoprotein 130 (gp130). Soluble gp130 (sgp130) is the natural inhibitor of IL-6 trans-signalling. The aim of this study was to test a possible influence of the gp130 genotype on sgp130 serum levels.
  
  
  METHODS
  In two separate populations, subjects were genotyped for the gp130 polymorphism G148C. Sgp130, IL-6 and soluble interleukin-6 receptor (sIL-6R) levels were measured. The OSLO population consisted of 546 male subjects at high risk for CAD. The VIENNA population consisted of 299 male subjects with angiographically proven CAD.
  
  
  RESULTS
  In the OSLO population, 124 (22.7%) subjects were hetero- or homozygote for the rare C allele. Individuals carrying the polymorphism had significantly higher levels of sgp130. In a multivariate linear regression model this association remained significant (adjusted p=0.001). In the VIENNA population, 48 (16.1%) subjects were hetero- or homozygote for the rare C allele. Consistent with the former study, sgp130 levels were significantly higher in carriers of the polymorphism compared to wildtype carriers (adjusted p=0.038). In the VIENNA population, sgp130 levels were significantly higher in diabetic patients. In the OSLO population, sgp130 was higher in patients with increased body mass index and in smokers (p<0.05).
  
  
  CONCLUSIONS
  Sgp130 serum levels are significantly higher in subjects carrying the gp130 polymorphism G148C compared to wildtype carriers. This finding proposes a possible genetical influence on sgp130 levels which may alter individual coping mechanisms in inflammatory diseases.
authors.affiliation: Department of Internal Medicine II, Medical University of Vienna, Vienna, Austria. Electronic address: anna.wonnerth@gmail.com.
authors.forename: Anna
authors.initials: A
authors.lastname: Wonnerth
authors.affiliation: Department of Internal Medicine II, Medical University of Vienna, Vienna, Austria; Ludwig Boltzmann Cluster for Cardiovascular Research.
authors.forename: Katharina M
authors.initials: KM
authors.lastname: Katsaros
authors.affiliation: Department of Internal Medicine II, Medical University of Vienna, Vienna, Austria.
authors.forename: Konstantin A
authors.initials: KA
authors.lastname: Krychtiuk
authors.affiliation: Department of Internal Medicine II, Medical University of Vienna, Vienna, Austria.
authors.forename: Walter S
authors.initials: WS
authors.lastname: Speidl
authors.affiliation: Department of Internal Medicine II, Medical University of Vienna, Vienna, Austria; Ludwig Boltzmann Cluster for Cardiovascular Research.
authors.forename: Christoph
authors.initials: C
authors.lastname: Kaun
authors.affiliation: Department of Internal Medicine II, Medical University of Vienna, Vienna, Austria.
authors.forename: Kylie
authors.initials: K
authors.lastname: Thaler
authors.affiliation: Ludwig Boltzmann Cluster for Cardiovascular Research; Department of Cardiology and Emergency Medicine, Wilhelminenspital, Vienna, Austria.
authors.forename: Kurt
authors.initials: K
authors.lastname: Huber
authors.affiliation: Department of Internal Medicine II, Medical University of Vienna, Vienna, Austria; Ludwig Boltzmann Cluster for Cardiovascular Research.
authors.forename: Johann
authors.initials: J
authors.lastname: Wojta
authors.affiliation: Department of Internal Medicine II, Medical University of Vienna, Vienna, Austria.
authors.forename: Gerald
authors.initials: G
authors.lastname: Maurer
authors.affiliation: Centre of Clinical Heart Research, Oslo University Hospital, Ulleval, Norway; Faculty of Medicine, University of Oslo, Norway.
authors.forename: Ingebjorg
authors.initials: I
authors.lastname: Seljeflot
authors.affiliation: Centre of Clinical Heart Research, Oslo University Hospital, Ulleval, Norway.
authors.forename: Harald
authors.initials: H
authors.lastname: Arnesen
authors.affiliation: Department of Internal Medicine II, Medical University of Vienna, Vienna, Austria; Department of Cardiology and Emergency Medicine, Wilhelminenspital, Vienna, Austria.
authors.forename: Thomas W
authors.initials: TW
authors.lastname: Weiss
mesh_terms: D000368:Aged; D019943:Amino Acid Substitution; D015331:Cohort Studies; D003545:Cysteine / Q000235:genetics; D050822:Cytokine Receptor gp130 / Q000097:blood*; D005787:Gene Frequency; D005998:Glycine / Q000235:genetics; D006023:Glycoproteins / Q000235:genetics*; D006801:Humans; D007249:Inflammation / Q000097:blood / Q000235:genetics; D015850:Interleukin-6 / Q000097:blood; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D019947:Receptors, Interleukin-6 / Q000097:blood
chemical_list: D006023:Glycoproteins; D015850:Interleukin-6; D019947:Receptors, Interleukin-6; C480482:glycoprotein 130, human; D050822:Cytokine Receptor gp130; D003545:Cysteine; D005998:Glycine
keywords: Coronary artery disease; Inflammation; Interleukin-6; Soluble interleukin-6 receptor