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Modification of the interleukin-6 response to air pollution by interleukin-6 and fibrinogen polymorphisms.

Ljungman P, Bellander T, Schneider A, Breitner S, Forastiere F, Hampel R, Illig T, Jacquemin B, Katsouyanni K, von Klot S, Koenig W, Lanki T, Nyberg F, Pekkanen J, Pistelli R, Pitsavos C, Rosenqvist M, Sunyer J, Peters A - Environ. Health Perspect. (2009)

Bottom Line: Nitrogen dioxide effects were consistently modified, but p-values for interaction were larger (0.09 and 0.19, respectively).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.

View Article: PubMed Central - PubMed

Affiliation: Department of Cardiology, Karolinska Institutet, Stockholm South Hospital, Stockholm, Sweden. petter.ljungman@ki.se

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).

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 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.

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Related in: MedlinePlus

Modification by IL6 rs2069832 and FGB rs1800790 genotypes of IL-6 response to increased ambient CO and NO2 in association with 6-hr exposure windows preceding blood sampling. Error bars indicate 95% CIs, and p-values are for significance of the interaction term. Interquartile ranges for 6-hr means: CO, 0.64 mg/m3; NO2, 11.5 μg/m3.*Heterogeneity of the city-specific effect estimates with a p-value < 0.1.
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f3-ehp-117-1373: Modification by IL6 rs2069832 and FGB rs1800790 genotypes of IL-6 response to increased ambient CO and NO2 in association with 6-hr exposure windows preceding blood sampling. Error bars indicate 95% CIs, and p-values are for significance of the interaction term. Interquartile ranges for 6-hr means: CO, 0.64 mg/m3; NO2, 11.5 μg/m3.*Heterogeneity of the city-specific effect estimates with a p-value < 0.1.

Mentions: Analyses of 6-hr exposure windows during the 24 hr immediately preceding blood sampling showed the clearest effect modification of the IL-6 response to CO within the three preceding 6-hr windows (Figure 3). We found greatest effect modification for FGB rs1800790 for increased CO during the 6–11 hr preceding sampling. The overall effect of a 2.2% increase in IL-6 per 0.64 mg/m3 increase of CO in this time window seemed again to be confined to individuals carrying the minor allele of FGB rs1800790, with a 10% (95% CI, 4.6–16%) increase in homozygotes (4% of study sample). In homozygotes for the major allele of IL6 rs2069832 (36% of the study sample), the corresponding increase was 3.6% (95% CI, 1.0–6.2%). Differences in the NO2 (Figure 3) and PM2.5 (data not shown) effects across genetic subgroups for different 6-hr exposure windows were similar but weaker. The distributed lag analyses restricted to subjects with at least one minor allele of FGB rs1800790 (GA or AA, 37% of study sample) or one major allele of IL6 2069832 (GA or AA, 83% of study sample) for 6-hr and 24-hr time windows showed associations with increased IL-6 for increases in CO for the 0–5 hr and 6–11 hr preceding sampling [see Supplemental Material, Figure 1 (doi: 10.1289/ehp.0800370.S1)]. The IL-6 increase seen in minor allele holders of FGB rs1800790 for 0–23 hr exposure of CO seemed to be mainly driven by exposure in the 6–11 hr time window. We found a similar but weaker pattern for 0–23 hr exposure in major allele holders of IL6 rs2069832.


Modification of the interleukin-6 response to air pollution by interleukin-6 and fibrinogen polymorphisms.

Ljungman P, Bellander T, Schneider A, Breitner S, Forastiere F, Hampel R, Illig T, Jacquemin B, Katsouyanni K, von Klot S, Koenig W, Lanki T, Nyberg F, Pekkanen J, Pistelli R, Pitsavos C, Rosenqvist M, Sunyer J, Peters A - Environ. Health Perspect. (2009)

Modification by IL6 rs2069832 and FGB rs1800790 genotypes of IL-6 response to increased ambient CO and NO2 in association with 6-hr exposure windows preceding blood sampling. Error bars indicate 95% CIs, and p-values are for significance of the interaction term. Interquartile ranges for 6-hr means: CO, 0.64 mg/m3; NO2, 11.5 μg/m3.*Heterogeneity of the city-specific effect estimates with a p-value < 0.1.
© Copyright Policy - public-domain
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC2737012&req=5

f3-ehp-117-1373: Modification by IL6 rs2069832 and FGB rs1800790 genotypes of IL-6 response to increased ambient CO and NO2 in association with 6-hr exposure windows preceding blood sampling. Error bars indicate 95% CIs, and p-values are for significance of the interaction term. Interquartile ranges for 6-hr means: CO, 0.64 mg/m3; NO2, 11.5 μg/m3.*Heterogeneity of the city-specific effect estimates with a p-value < 0.1.
Mentions: Analyses of 6-hr exposure windows during the 24 hr immediately preceding blood sampling showed the clearest effect modification of the IL-6 response to CO within the three preceding 6-hr windows (Figure 3). We found greatest effect modification for FGB rs1800790 for increased CO during the 6–11 hr preceding sampling. The overall effect of a 2.2% increase in IL-6 per 0.64 mg/m3 increase of CO in this time window seemed again to be confined to individuals carrying the minor allele of FGB rs1800790, with a 10% (95% CI, 4.6–16%) increase in homozygotes (4% of study sample). In homozygotes for the major allele of IL6 rs2069832 (36% of the study sample), the corresponding increase was 3.6% (95% CI, 1.0–6.2%). Differences in the NO2 (Figure 3) and PM2.5 (data not shown) effects across genetic subgroups for different 6-hr exposure windows were similar but weaker. The distributed lag analyses restricted to subjects with at least one minor allele of FGB rs1800790 (GA or AA, 37% of study sample) or one major allele of IL6 2069832 (GA or AA, 83% of study sample) for 6-hr and 24-hr time windows showed associations with increased IL-6 for increases in CO for the 0–5 hr and 6–11 hr preceding sampling [see Supplemental Material, Figure 1 (doi: 10.1289/ehp.0800370.S1)]. The IL-6 increase seen in minor allele holders of FGB rs1800790 for 0–23 hr exposure of CO seemed to be mainly driven by exposure in the 6–11 hr time window. We found a similar but weaker pattern for 0–23 hr exposure in major allele holders of IL6 rs2069832.

Bottom Line: Nitrogen dioxide effects were consistently modified, but p-values for interaction were larger (0.09 and 0.19, respectively).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.

View Article: PubMed Central - PubMed

Affiliation: Department of Cardiology, Karolinska Institutet, Stockholm South Hospital, Stockholm, Sweden. petter.ljungman@ki.se

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).

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 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.

Show MeSH
Related in: MedlinePlus