Grantee Research Project Results
Epigenetic Markers of Exposure to Traffic and Pediatric AsthmaEPA Grant Number: FP917367
Title: Epigenetic Markers of Exposure to Traffic and Pediatric Asthma
Investigators: Sebastian, Kelly J
Institution: University of Cincinnati
EPA Project Officer: Cobbs-Green, Gladys M.
Project Period: September 1, 2011 through August 31, 2014
Project Amount: $126,000
RFA: STAR Graduate Fellowships (2011)
Research Category: Fellowship - Human Health: Public Health Sciences , Academic Fellowships
Although epigenetics has become an intriguing area of research concerning the development of childhood asthma, significant questions remain regarding epigenetic biomarkers of traffic-related air pollution and the critical timing of early-life exposure. This research project will investigate the relationship between diesel exhaust particle exposure and the methylation status of key asthma-related genes and surrogate markers of global methylation. In addition, this project will determine whether these epigenetic changes are associated with the development of allergic disease and asthma over time.Approach:
The first phase of this project is to identify and test the utility of salivary epigenetic markers as biomarkers of DEP exposure in the Cincinnati Childhood Allergy and Air Pollution Study (CCAAPS) cohort. The methylation status of the promoter region of IFN-γ and global methylation status of LINE1 and AluYb8, examined via pyrosequencing, will be explored among children exposed to varying levels of DEP. This study will be the first to utilize saliva as a DNA source to experimentally determine methylation profiles with respect to DEP exposure and pediatric asthma. If proven to be successful, this methodology would be critically important for advancing epidemiologic studies in large cohorts, especially those studying environmental exposures and childhood asthma. The second phase is to determine if allergic sensitization and/or asthma during childhood is associated with methylation of the IFN-γ promoter and/or LINE1/AluYb8. The CCAAPS cohort has been clinically examined annually at ages 1 through 4 and at age 7 for the development of allergic disease phenotypes and asthma.Expected Results:
Expression of IFN-γ has been shown to be regulated by DNA methylation. Thus, it is hypothesized that the DNA methylation status of the IFN-γ gene promoter region will be hypermethylated among children exposed to high levels of DEP compared to children exposed to low levels of DEP. Demethylation of LINE1 and Alu elements increases their activity as retrotransposable sequences, which may induce genomic alterations and ultimately deregulate gene transcription. Therefore, this study believes LINE1 and/or AluYb8 will be hypomethylated among children with high DEP levels compared to children with low DEP levels. Further, it is theorized that the methylation status will be significantly associated with allergic disease and asthma development.
Potential to Further Environmental / Human Health Protection
There have been minimal well-designed epidemiologic studies of ambient air pollution and the epigenome addressing the numerous allergic outcomes seen in pediatric asthma. Studies within well-established longitudinal cohorts like CCAAPS, which have tracked lifetime childhood exposure to traffic-related air pollution and the development of allergic health phenotypes and asthma, are needed. This study will potentially identify biomarkers of diesel exhaust exposure and susceptible populations by means of epigenotyping and will not only provide new measures for exposure and disease surveillance, prevention and management but also new insights into critical periods of airway development, asthma etiology and asthma severity.Supplemental Keywords:
diesel exhaust particles, pediatric asthma, epigenetics, DNA methylation, global methylation, gene-specific methylation