Ljungman Petter, Bellander Tom, Schneider Alexandra, Breitner Susanne, Forastiere Francesco, Hampel Regina, Illig Thomas, Jacquemin Bénédicte, Katsouyanni Klea, von Klot Stephanie, Koenig Wolfgang, Lanki Timo, Nyberg Fredrik, Pekkanen Juha, Pistelli Riccardo, Pitsavos Christos, Rosenqvist Mårten, Sunyer Jordi, Peters Annette
Department of Cardiology, Karolinska Institutet, Stockholm South Hospital, Stockholm, Sweden.
Environ Health Perspect. 2009 Sep;117(9):1373-9. doi: 10.1289/ehp.0800370. Epub 2009 Apr 6.
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).
We investigated whether IL6 and fibrinogen gene variants can affect plasma IL-6 responses to air pollution in patients with cardiovascular disease.
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.
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.
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.
有证据表明空气污染对心血管的影响是由炎症介导的，并且空气污染可诱导白细胞介素-6基因（IL6）的基因表达。
我们调查了IL6和纤维蛋白原基因变异是否会影响心血管疾病患者血浆IL-6对空气污染的反应。
我们对来自欧洲六个城市的955名心肌梗死幸存者（共5539次测量）反复测定血浆IL-6。我们使用加性混合模型进行特定城市分析，该模型对患者特征、时间趋势和天气进行了调整，以评估空气污染物对血浆IL-6的影响。我们使用荟萃分析方法汇总特定城市的估计值。我们从IL6中选择了三个单核苷酸多态性（SNP），并分别从纤维蛋白原α链基因（FGA）和β链基因（FGB）中选择了一个SNP进行基因-环境分析。
我们发现，暴露于一氧化碳（CO；24小时平均值）后，IL6 rs2069832和FBG rs1800790变异的改变最为一致（交互作用的p值分别为0.034和0.019）。二氧化氮的影响也有一致的改变，但交互作用的p值更大（分别为0.09和0.19）。暴露后6-11小时观察到最强的影响，例如，对于FGB rs1800790的次要纯合子，每0.64 mg/m³ CO使IL-6总体增加2.2%的效应被改变为IL-6增加10%（95%置信区间，4.6-16%）（交互作用的p值 = 0.002）。
与交通相关的气态空气污染对炎症的影响在患有缺血性心脏病的遗传亚群中可能更强。这一信息可能为识别出比其他患者能从更清洁的环境和抗炎治疗中获益更多的心肌梗死后患者提供机会。
