Over the past two decades asthma morbidity among children has increased dramatically, with disproportionate morbidity among Hispanic and African-Americans. Environmental factors (allergens, fungi, environmental tobacco smoke, air contaminants, cold air, etc.) are known to be associated with asthma severity in children. More recently genetic factors have been proposed as important determinants in the severity of asthma. The interaction of specific mutations within genes with specific environmental factors, however, is poorly understood despite its crucial importance in understanding asthma severity. In this application we seek to expand our asthma severity study to examine the gene-environment interactions in modifying asthma severity. The asthmatic children (14 percent Black, 27 percent Hispanic, 55 percent, Caucasian, 4 percent Other and 16 percent of mothers with an education level of less than 12 years of schooling) are currently being followed to test the hypothesis that carefully quantified indoor allergen exposures (house dust mite, cat, dog, cockroach and fungi) and air contaminant exposures (environmental tobacco smoke, nitrogen dioxide, nitrous acid, ozone, fine particle mass and pollen) are associated with asthma severity (daily respiratory symptoms, medication use, and utilization of health care services and lung function) in a population of 1,002 physician diagnosed asthmatic children between 5 and 12 years of age whose health status familial history, home environment, and potential confounders are carefully characterized. In this application we will investigate the respective roles of allergens, ETS and other air contaminant exposures and the presence of polymorphisms in the beta2 adrenergic receptor (Arg 16-Gly or Gln27-Glu) and in the promoter region of the IL-4 gene, particularly the TT polymorphism, in asthma severity while controlling for allergic status of the child. Although several candidate genes have been identified as potential genetic determinants of asthma severity, we chose beta2-AR and IL-4 polymorphisms as the initial genes to examine in this population because they have been linked to asthma severity. By collecting and storing blood samples, other candidate genes could be examined, as they are prioritized. Our extensive characterization of environmental exposures and risk factors for a large diverse population of asthmatic children, provide a unique population within which gene-environment interactions in the severity of asthma can be examined. This study will provide a basis to prioritizing environmental interventions to reduce asthma morbidity in children.
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