TY - JOUR
TI - Modification of the interleukin-6 response to air pollution by interleukin-6 and fibrinogen polymorphisms
AU - Ljungman, P.
AU - Bellander, T.
AU - Schneider, A.
AU - Breitner, S.
AU - Forastiera, F.
AU - Hampel, R.
AU - Illig, T.
AU - Jacquemin, B.
AU - Katsouyanni, K.
AU - von Klot, S.
AU - Koenig, W.
AU - Lanki, T.
AU - Nyberg, F.
AU - Pekkanen, J.
AU - Pistelli, R.
AU - Pitsavos, C.
AU - Rosenqvist, M.
AU - Sunyer, J.
AU - Peters, A.
JO - Environmental Health Perspectives
PY - 2009
VL - 117
TODO - 9
SP - 1373-1379
PB - 
SN - 0091-6765, 1552-9924
TODO - 10.1289/ehp.0800370
TODO - carbon monoxide;  fibrinogen;  interleukin 6;  nitrogen dioxide, adult;  aged;  air pollutant;  air pollution;  alpha chain;  article;  beta chain;  cardiovascular disease;  environmental exposure;  environmental factor;  Europe;  female;  gene interaction;  genotype;  heart infarction;  homozygote;  human;  major clinical study;  male;  methodology;  priority journal;  protein blood level;  single nucleotide polymorphism;  survivor;  weather, Aged;  Air Pollution;  Carbon Monoxide;  Female;  Fibrinogen;  Humans;  Interleukin-6;  Male;  Middle Aged;  Myocardial Infarction;  Nitrogen Dioxide;  Polymorphism, Single Nucleotide
TODO - 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). Objectives: 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 α-chain gene (FGA) and β-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/m3 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.
ER -