Modification of the interleukin-6 response to air pollution by interleukin-6 and fibrinogen polymorphisms.
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.
Ljungman
Petter
P
Department of Cardiology, Karolinska Institutet, Stockholm South Hospital, Stockholm, Sweden. petter.ljungman@ki.se
Bellander
Tom
T
Schneider
Alexandra
A
Breitner
Susanne
S
Forastiere
Francesco
F
Hampel
Regina
R
Illig
Thomas
T
Jacquemin
Bénédicte
B
Katsouyanni
Klea
K
von Klot
Stephanie
S
Koenig
Wolfgang
W
Lanki
Timo
T
Nyberg
Fredrik
F
Pekkanen
Juha
J
Pistelli
Riccardo
R
Pitsavos
Christos
C
Rosenqvist
Mårten
M
Sunyer
Jordi
J
Peters
Annette
A
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
D015850:Interleukin-6; D002248:Carbon Monoxide; D005340:Fibrinogen; D009585:Nitrogen Dioxide