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Atopic asthma is a complex disease process that has a significant social, personal and economic burden across all ages. Leukotriene-receptors are involved in the cascade of inflammation that may result in symptoms of atopy and asthma. Two leukotriene receptors have been identified in the lung. The cysteinyl leukotriene receptor 1 and cysteinyl leukotriene receptor 2 genes (i.e., CYSLTR1 and CYSLTR2) have been sequenced, and a number of single nucleotide polymorphisms (SNPs) within these genes have been identified.The purpose of this study was to: (1) Determine the relationship between CYSLTR1 genotypes, CYSLTR2 genotype, atopy, elevated IgE level, and eosinophilia, (2) Determine the relationship between CYSLTR1 genotypes, CYSLTR2 genotype, asthma, and atopic asthma, and (3) Determine the degree of interaction between CYSLTR2 genetic variation and gender in atopic asthma.Nested within two sub-studies of the Tucson Epidemiological Study of Airway Obstructive Disease (TESAOD) study, a prospective longitudinal cohort, 853 individuals were entered into this study. Study criteria included Non-Hispanic white adults, who consented to genetic testing in the two sub-studies. Tagging SNPs of the CYSLTR1 and CYSLTR2 genes were genotyped. Serum IgE status and eosinophilia were obtained from existing dataset. Questionnaires collected in the parent study were used to obtain demographic and clinical data.SNP rs321006 in the CYSLTR1 gene was associated with atopy among Non-Hispanic white women. Assuming a recessive model, among female Non-Hispanic white adults, the odds of having rs321073 CC genotype was 5.82 times higher among those with atopic asthma than those without atopic asthma. No gene by gender interaction was found between SNP of interest in CYSLTR2 and atopic asthma. Genetic association of SNPs rs321006 with atopy and rs321073 with atopic asthma are novel findings to date.Implications for nurses, clinicians, and scientists include better understanding of associations of these genetic variations with asthma, atopy, and atopic asthma that can generate further inquiry into other mechanisms of atopic asthma. These novel genetic associations with atopy and atopic asthma may have the potential for personalized medicine that might afford patients with appropriate treatment based on their genotype.

<p>Asthma is a lung disease characterized by wide variations in airflow over short periods of time. Exacerbations of asthma can be accompanied by symptoms of chest tightness, shortness of breath and wheezing; airway inflammation characterized by an influx of eosinophils and/or neutrophils; and the expression of pro-inflammatory cytokines in the airway. There is strong evidence supporting a central role for the T cell in asthma. In atopic asthma, T cells are documented components of the late-phase response to inhaled allergen, driving airway inflammation, mucus hypersecretion, and bronchoconstriction through the release of cytokines and other mediators. T cells have also been shown to produce inflammatory cytokines in response to allergen in nonatopic asthmatics, indicating a potential role in mediating disease in this phenotype. In both atopic and nonatopic asthma, aberrant T cell responses to allergen may drive the infiltration of neutrophils and eosinophils into the airway through the production of pro- inflammatory cytokines, leading to exacerbations of disease. This project has investigated the role of several T cell cytokines in driving disease and acting as biomarkers in asthma: interleukin-5, interleukin-17A, interleukin-23, interleukin- 10, and interferon-γ. We have measured allergen-induced cytokine production by peripheral blood mononuclear cells (PBMCs) and examined its ability to distinguish between different asthma phenotypes: asthma vs normal, atopic vs nonatopic asthma, eosinophilic bronchitis vs noneosinophilic bronchitis, and neutrophilic vs nonneutrophilic bronchitis. Our data shows that allergen-induced peripheral blood mononuclear cell responses to allergen are not good biomarkers of disease in asthma. No differences in PBMC cytokine production are seen in patients with asthma, compared with normal controls, or between patients with different asthmatic phenotypes. It is not possible to determine a patient’s disease state, atopic status, or type of bronchitis by examining their PBMC cytokine responses to allergen.</p> / Master of Science (MSc)