DIFFERENTIAL SUSCEPTIBILITY OF REPETITIVE ELEMENTS TO AIRBORNE POLLUTANTS

Background. Repetitive elements take up >40% of the human genome and can change distribution through transposition, thus generating subfamilies. Repetitive element DNA methylation has been associated with several diseases and environmental exposures, including exposure to airborne pollutants. No systematic analysis has yet been conducted to examine the effects of exposures across different repetitive element subfamilies. Objective. To evaluate sensitivity of DNA methylation and expression in differentially‐evoluted LINE, Alu, and HERV subfamilies to different types of airborne pollutants. Methods. We sampled a total of 120 male participants from three studies (20 high-, 20 low-exposure in each study) of steel workers exposed to metal-rich particulate matter (measured as PM10) (Study 1); gas-station attendants exposed to air benzene (Study 2); and truck drivers exposed to traffic-derived elemental carbon (Study 3). We measured methylation by bisulfite-PCR-pyrosequencing in 10 differentially‐evoluted repetitive element subfamilies. We evaluate sensitivity of DNA methylation of the same 10 subfamilies and the expression of the most representative and well studied subfamilies AluSx and L1HS in a more wide population of 120 individuals (Beijing Truck Driver Air Pollution Study, BTDAS) with a well characterized personal exposure levels of PM2.5 and ambient PM10. Results. In the three studies, high-exposure groups exhibited subfamily-specific methylation differences compared to low-exposure groups: L1PA2 showed lower DNA methylation in steel workers (P=0.04) and gas station attendants (P=0.03); L1Ta showed lower DNA methylation in steel workers (P=0.02); AluYb8 showed higher DNA methylation in truck drivers (P=0.05). Within each study, dose-response analyses showed subfamily-specific correlations of methylation with exposure levels. Interaction models showed that the effects of the exposures on DNA methylation were dependent on the subfamily evolutionary age, with stronger effects on older LINEs from PM10 (p‐interaction=0.003) and benzene (p‐interaction=0.04), and on younger Alus from PM10 (p-interaction=0.02). In the BTDA Study the group analysis showed a significantly lower DNA methylation in the truck drivers group in AluSx (P=0.02) and MLT1d (P=0.01). The dose response analysis confirmed a lower AluSx methylation in relation to PM10 8-day mean (P=0.047) and a lower MLT1d methylation in relation to exposure to PM2.5 (P=0.002), EC (P=0.008), ambient PM10 study day mean (P=0.005) and ambient PM10 8-day mean (P=0.018). Conclusions. The evolutionary age of repetitive element subfamilies determines differential susceptibility of DNA methylation and expression to airborne pollutants.