title: Genetic predisposition of the interleukin-6 response to inflammation: implications for a variety of major diseases?
abstract: BACKGROUND
  A single-nucleotide polymorphism (SNP) in the promoter region of the interleukin-6 (IL-6) gene at position -174 (G>C) has been reported to be associated with a variety of major diseases, such as Alzheimer disease, atherosclerosis, and cardiovascular disease, cancer, non-insulin-dependent diabetes mellitus, osteoporosis, sepsis, and systemic-onset juvenile chronic arthritis. However, authors of previous in vitro and in vivo studies have reported conflicting results regarding the functionality of this polymorphism. We therefore aimed to clarify the role of the -174 SNP for the induction of IL-6 in vivo.
  
  
  METHODS
  We vaccinated 20 and 18 healthy individuals homozygous for the -174 C and G alleles, respectively, with 1 mL of Salmonella typhii vaccine. IL-1beta, IL-6, and tumor necrosis factor-alpha (TNF-alpha) were measured in the blood at baseline and up to 24 h after vaccination.
  
  
  RESULTS
  Individuals with the G genotype had significantly higher plasma IL-6 values at 6, 8, and 10 h after vaccination than did individuals with the C genotype (P <0.005). There were no differences between the two genotypes regarding serum concentrations of IL-1beta and TNF-alpha before or after vaccination.
  
  
  CONCLUSIONS
  The -174 G>C SNP in the promoter region of the IL-6 gene is functional in vivo with an increased inflammatory response associated with the G allele. Considering the central role of IL-6 in a variety of major diseases, the present finding might be of major relevance.
authors.affiliation: Department of Medicine, Danderyd University Hospital, Stockholm, Sweden. marie.bennermo@ds.se
authors.forename: Marie
authors.initials: M
authors.lastname: Bennermo
authors.forename: Claes
authors.initials: C
authors.lastname: Held
authors.forename: Sten
authors.initials: S
authors.lastname: Stemme
authors.forename: Carl-Göran
authors.initials: CG
authors.lastname: Ericsson
authors.forename: Angela
authors.initials: A
authors.lastname: Silveira
authors.forename: Fiona
authors.initials: F
authors.lastname: Green
authors.forename: Per
authors.initials: P
authors.lastname: Tornvall
mesh_terms: D005260:Female; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D007249:Inflammation / Q000235:genetics* / Q000276:immunology; D007375:Interleukin-1 / Q000097:blood; D015850:Interleukin-6 / Q000096:biosynthesis* / Q000097:blood; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D011401:Promoter Regions, Genetic; D022562:Salmonella Vaccines / Q000276:immunology; D014409:Tumor Necrosis Factor-alpha / Q000032:analysis
chemical_list: D007375:Interleukin-1; D015850:Interleukin-6; D022562:Salmonella Vaccines; D014409:Tumor Necrosis Factor-alpha