Prenatal Tobacco Smoke, Genetic and Epigenetic Changes, and Respiratory Health

Asthma is a leading cause of childhood morbidity and normal lung function development is essential for respiratory health during childhood and subsequent adult life. We have developed preliminary data that highlight the adverse effects of prenatal tobacco smoke (PTS) exposure. PTS exposure can permanently alter the developing lung and fetal immune function, increasing risk for respiratory disease, and understanding the mechanisms of these effects may shed light on the effects of other environmental exposures. Scientists have clearly demonstrated both early-life environmental and genetic factors contribute to the pathogenesis of asthma and lung function. Recent studies highlight the importance of genetic variants and epigenetic alterations underlying environmentally-related immune function and respiratory health. We present preliminary studies showing the potential importance of genetic and epigenetic variation in the TAM (TYRO3, AXL, and MER) family of Type I receptor tyrosine kinases in early life lung function and asthma pathogenesis in the context of PTS. To provide a conceptual framework useful for addressing this critical knowledge gap, we propose an integrated epigenetic-genetic analysis of the TAM (TYRO3, AXL, and MER) family of Type I receptor tyrosine kinases to better understand the biological mechanisms underlying the impaired lung function development and increased risk of asthma associated with PTS. Specifically, this application builds on the PI’s K01 project to further evaluate 1500 subjects in the Children’s Health Study (CHS), a longitudinal study of air pollutant and respiratory health in 16 Southern California communities. The study will leverage an existing comprehensive resource that includes genome-wide association data, linked birth records, and extensive respiratory assessments.