Epigene-environment Interactions and Fibrinogen in an Elderly Cohort: Veterans Administration Normative Aging Study

Abstract

O-31A3-2 Background/Aims: In a previous study, we observed positive effects of traffic-related pollutants (PN, BC, NO2, and CO) on fibrinogen. Epigenetics refers to potentially mutable marks on the chromosome that influence gene expression, including DNA methylation. These methylation patterns have been shown to influence disease. This is the first study to investigate an epigene-environment interaction for the effects of air pollution on levels of fibrinogen, a key player in the clotting cascade, in the elderly, a suspected risk group. Methods: Using the 75th percentile of the baseline LINE-1 methylation distribution as a cut-off point, we created 2 categories (low vs. high LINE-1 methylation). We fit separate mixed models with random intercepts stratified by these 2 levels. We adjusted for age, seasonality, body mass index, day of the week, temperature, relative humidity, smoking status, statin use, and diabetes, percent neutrophil in differential blood count, and batch for DNA methylation analysis. We investigated whether global LINE-1 methylation modifies the effect of air pollution on fibrinogen levels in 705 elderly men participating in the Veterans Administration Normative Aging Study (2000–2008). We evaluated differences of fibrinogen increase (δ_low vs. high) per 1 interquartile range increase of pollutant between the 2 groups and computed a test of significance of that difference. Results: In all subjects, we observed significant associations of 3 and 7 days moving average (MA3 and MA7) black carbon levels with fibrinogen (P = 0.021 and P = 0.029, respectively). Among participants with low LINE-1 methylation, we also found that the effect of black carbon on fibrinogen was significantly greater compared to subjects with higher LINE-1 DNA methylation (δ low vs high = 5.0%, P interaction = 0.035 for MA3 and δ low vs. high = 5.7%, P interaction = 0.036 for MA7). Conclusion: We observed greater effects of air pollutants on fibrinogen levels among subjects with lower LINE-1 methylation, indicating that epigenetic status can convey susceptibility to air pollution.