AdvisorWright, Anne L.
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PublisherThe University of Arizona.
RightsCopyright © is held by the author. Digital access to this material is made possible by the University Libraries, University of Arizona. Further transmission, reproduction or presentation (such as public display or performance) of protected items is prohibited except with permission of the author.
AbstractBACKGROUND: The prevalence of childhood asthma has been increasing worldwide. Modern societal exposures that have been implicated as possible causes of this increase include more hygienic lifestyles, antibiotic usage, and vitamin D deficiency. While there is much evidence that the origins of allergic disease begin in infancy, the uncertainty of asthma diagnosis in the first few years of life makes it difficult to assess the impact of early environmental exposures in very young children, and intermediate phenotypes that might assist in this assessment are lacking. An additional challenge to allergic disease research is the potential for gene-by-environment interactions, in which specific exposures differentially affect children depending on genotype. The objectives of this study were to assess relations of allergic disease outcomes (total IgE, specific IgE and asthma) with: 1) exposures related to modern lifestyle including day-care, antibiotic use and vitamin D levels; 2) cytokine profiles as a potential intermediate phenotypes; and 3) day-care exposure in the context of a relevant genotype.METHODS: This study utilizes data from a birth cohort. Allergic outcomes were assessed longitudinally through 5 years. Exposure data was collected by interview, or via blood samples in the case of vitamin D, cytokines, and genotype. Relations were assessed using longitudinal analysis techniques.RESULTS: Day-care was associated with decreased total and specific IgE through age 5. Antibiotics use was not associated with any outcome. Vitamin D levels showed 1) a U-shaped association with total and specific IgE, such that both high and low levels conveyed greater risk; and 2) no association with asthma. Cytokine profiles at 3 months of age, but not at birth, were predictive of total IgE and asthma. Finally, a significant gene-by-environment interaction was found between day-care and the TLR2/-16934 gene, such that the protective day-care relation occurred only for children carrying a T-allele.CONCLUSION: This study provides evidence that childhood allergic disease is inversely associated with day-care exposure and has a U-shaped relation with 25(OH)D levels at birth. It demonstrates that cytokine profiles as early as 3 months predict allergic outcomes through age 5 years, and finally, provides an example of a gene-by-environment interaction.
Degree ProgramGraduate College