TY - JOUR T1 - LATE-BREAKING ABSTRACT: NO<sub>2</sub> and lung function: Mediation by DNA methylation JF - European Respiratory Journal JO - Eur Respir J DO - 10.1183/13993003.congress-2016.PA1212 VL - 48 IS - suppl 60 SP - PA1212 AU - Ana Julia de Faria Coimbra Lichtenfels AU - Diana A. van der Plaat AU - Kim de Jong AU - Ronald P. Stolk AU - Bert Brunekreef AU - Judith M. Vonk AU - H. Marike Boezen Y1 - 2016/09/01 UR - http://erj.ersjournals.com/content/48/suppl_60/PA1212.abstract N2 - Background: Ambient levels of NO2 exposure are consistently associated with a higher risk for respiratory exacerbations and lower lung function, but the mechanisms underlying this association are not clear. Possibly, differential DNA methylation associated with NO2 exposure may play a mediating role in this.Aim: Assess whether differential DNA methylation mediates the effect of NO2 exposure on lung function.Methods: 1017 subjects of the LifeLines cohort study, a large general population based cohort in the north of the Netherlands, were included. Blood-DNA methylation expressed as β-value was assessed using Illumina Methylation 450K chips. Outdoor annual mean concentration of NO2 at the participant's home address was estimated using Land Use Regression (LUR) models.Results: A 10 µg/m3 increase in NO2 concentration was marginally associated with higher levels of FEV1/FVC (B=1.483, p=0.055). No significant association between NO2 and FEV1, FVC and FEF25-75 was found. Adjusted robust linear regression models, assessing 430,950 CpG probes, revealed significant associations between NO2 exposure and 8 CpGs sites (Bonferroni corrected threshold: p &lt; 1.16E-7) mapping to 8 genes. Two of these CpGs sites were also strongly and positively associated with FEV1/FVC, but no mediation effect was seen (assessed with the Sobel test).Conclusion: Although no mediation effect was found, NO2 exposure was associated with differential methylation in CpGs that were positively associated with lung function. Since the level of NO2 exposure in LifeLines is very low, replication of these findings is needed in other cohort studies with a broader range of exposure. ER -