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A4607 - DNA Methylation Mediates Effect of Early-Life Chest Illness on Asthma Among Minority Children
Author Block: S. Oh1, D. Hu1, C. Eng1, S. Huntsman1, J. Liberto1, P. Goddard1, L. Borrell2, J. Rodriguez-Santana3, H. J. Farber4, P. Avila5, R. Kumar6, E. Brigino-Buenaventura7, A. Davis8, M. LeNoir9, K. Meade8, S. Sen1, F. Lurmann10, W. Rodriguez-Cintron11, S. Thyne12, D. Serebrisky13, E. G. Burchard1; 1UCSF, San Francisco, CA, United States, 2City University of New York, New York, NY, United States, 3Centro de Neumologia Pediatrica, San Juan, PR, United States, 4Pulmonary Medicine Service, Texas Children's Hospital, Houston, TX, United States, 5Northwestern University, Chicago, IL, United States, 6Childrens Memorial Hosp, Chicago, IL, United States, 7Kaiser Permanente-Vallejo Medical Center, Vallejo, CA, United States, 8Children's Hospital and Research Center Oakland, Oakland, CA, United States, 9Bay Area Pediatrics, Oakland, CA, United States, 10Sonoma Technologies, Inc., Petaluma, CA, United States, 11Veterans Caribbean Health Care System, San Juan, PR, United States, 12UCLA Medical Center, Los Angeles, CA, United States, 13Jacobi Medical Center, Bronx, NY, United States.
Rationale: Epidemiological studies have made clear the strong relationship between severe early-life respiratory illnesses and development of asthma. Specifically, links between early-life respiratory syncytial virus (RSV) infection and asthma development are strong. We have shown that the proportion of children with asthma who reported bronchiolitis/RSV in early life was 4- to 9-fold higher among Puerto Ricans (10.5%) than African Americans (2.6%) and Mexicans (1.2%), and that the odds for asthma were consistently highest among Puerto Ricans (odds ratio [OR] = 6.6, 95%CI: 3.3-13.9) compared with Mexicans (OR = 2.1, 95%CI: 0.5-10.0) and African Americans (OR = 2.6, 95%CI: 0.5-19.5). Viral infections produce distinct changes to the epigenome and epigenetic modifications are known to modify asthma and regulate allergic diseases. We therefore hypothesized that epigenetic modifications may mediate the effect of early-life respiratory illness on asthma status. Methods: We studied a sample of 560 participants from the GALA II (Genes-Environments and Admixture in Latino Americans) study. Chest illnesses included bronchitis, cold, and bronchiolitis. We measured the methylation status of more than 450,000 CpG loci across the genome using whole blood samples. Covariates included age, sex, ethnicity, number of siblings, maternal education and smoking during pregnancy, and cell composition. We performed mediation analysis to estimate the extent to which DNA methylation explains the association between physician-diagnosed asthma and reported chest illness in the first two years of life. We also performed pathway analyses based on significant results from our mediation analysis. Results and Conclusions: We identified several Bonferroni-significant CpG loci that mediated the effect of early-life respiratory illness on asthma status, and these associations appeared to vary by ethnic subgroup. The CpG loci mapped to biologically relevant pathways and genes involved in vesicle transport, production of viral components, alveolar inflammation, and RNA transport. Our preliminary results indicate that DNA methylation mediates the effect of early-life respiratory viral infections on asthma status among Latino children, and that the effects may be population-specific.