title: Modification of the interleukin-6 response to air pollution by interleukin-6 and fibrinogen polymorphisms.
abstract: BACKGROUND
  Evidence suggests that cardiovascular effects of air pollution are mediated by inflammation and that air pollution can induce genetic expression of the interleukin-6 gene (IL6).
  
  
  OBJECTIVE
  We investigated whether IL6 and fibrinogen gene variants can affect plasma IL-6 responses to air pollution in patients with cardiovascular disease.
  
  
  METHODS
  We repeatedly determined plasma IL-6 in 955 myocardial infarction survivors from six European cities (n = 5,539). We conducted city-specific analyses using additive mixed models adjusting for patient characteristics, time trend, and weather to assess the impact of air pollutants on plasma IL-6. We pooled city-specific estimates using meta-analysis methodology. We selected three IL6 single-nucleotide polymorphisms (SNPs) and one SNP each from the fibrinogen alpha-chain gene (FGA) and beta-chain gene (FGB) for gene-environment analyses.
  
  
  RESULTS
  We found the most consistent modifications for variants in IL6 rs2069832 and FBG rs1800790 after exposure to carbon monoxide (CO; 24-hr average; p-values for interaction, 0.034 and 0.019, respectively). Nitrogen dioxide effects were consistently modified, but p-values for interaction were larger (0.09 and 0.19, respectively). The strongest effects were seen 6-11 hr after exposure, when, for example, the overall effect of a 2.2% increase in IL-6 per 0.64 mg/m(3) CO was modified to a 10% (95% confidence interval, 4.6-16%) increase in IL-6 (p-value for interaction = 0.002) for minor homozygotes of FGB rs1800790.
  
  
  CONCLUSIONS
  The effect of gaseous traffic-related air pollution on inflammation may be stronger in genetic subpopulations with ischemic heart disease. This information could offer an opportunity to identify postinfarction patients who would benefit more than others from a cleaner environment and antiinflammatory treatment.
authors.affiliation: Department of Cardiology, Karolinska Institutet, Stockholm South Hospital, Stockholm, Sweden. petter.ljungman@ki.se
authors.forename: Petter
authors.initials: P
authors.lastname: Ljungman
authors.forename: Tom
authors.initials: T
authors.lastname: Bellander
authors.forename: Alexandra
authors.initials: A
authors.lastname: Schneider
authors.forename: Susanne
authors.initials: S
authors.lastname: Breitner
authors.forename: Francesco
authors.initials: F
authors.lastname: Forastiere
authors.forename: Regina
authors.initials: R
authors.lastname: Hampel
authors.forename: Thomas
authors.initials: T
authors.lastname: Illig
authors.forename: Bénédicte
authors.initials: B
authors.lastname: Jacquemin
authors.forename: Klea
authors.initials: K
authors.lastname: Katsouyanni
authors.forename: Stephanie
authors.initials: S
authors.lastname: von Klot
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Koenig
authors.forename: Timo
authors.initials: T
authors.lastname: Lanki
authors.forename: Fredrik
authors.initials: F
authors.lastname: Nyberg
authors.forename: Juha
authors.initials: J
authors.lastname: Pekkanen
authors.forename: Riccardo
authors.initials: R
authors.lastname: Pistelli
authors.forename: Christos
authors.initials: C
authors.lastname: Pitsavos
authors.forename: Mårten
authors.initials: M
authors.lastname: Rosenqvist
authors.forename: Jordi
authors.initials: J
authors.lastname: Sunyer
authors.forename: Annette
authors.initials: A
authors.lastname: Peters
mesh_terms: D000368:Aged; D000397:Air Pollution; D002248:Carbon Monoxide / Q000032:analysis; D005260:Female; D005340:Fibrinogen / Q000235:genetics*; D006801:Humans; D015850:Interleukin-6 / Q000097:blood / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D009203:Myocardial Infarction / Q000097:blood; D009585:Nitrogen Dioxide / Q000032:analysis; D020641:Polymorphism, Single Nucleotide
chemical_list: D015850:Interleukin-6; D002248:Carbon Monoxide; D005340:Fibrinogen; D009585:Nitrogen Dioxide