GENE-ENVIRONMENT INTERACTIONS IN ASTHMA DEVELOPMENT

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DESCRIPTION: Asthma is a major chronic disease in the U.S. and the most common chronic illness of childhood. The Centers for Disease Control estimate that the prevalence of asthma has increased 75 percent between 1980 and 1994, with disproportionate morbidity and mortality among Hispanic and African-Americans. Genetic and environmental factors are known to be important risk factors in asthma development. The interaction of specific mutations within genes with specific environmental factors (allergens, fungi, environmental tobacco smoke, etc.,), however, is poorly understood despite its crucial importance in understanding the development of asthma. In this competitive renewal application we seek to continue to follow our population of 1,002 children (549 White, 268 Hispanic, 139 African American, and 46 Other), enrolled at birth, to test the original hypothesis that carefully quantitated environmental factors (indoor allergens and environmental tobacco smoke, ETS, exposures) are associated with the incidence of asthma in children whose health status, familial history, antigen-specific IgE status, home environment, and potential confounders are carefully characterized. We have followed 103 of the children for 3 years, 508 for 2 years and 391 for one year. During the first year of life, episodes of wheeze, persistent cough, and shortness of breath were recorded for 42, 49 and 21 percent of the children. Thus far, 180 children have been reported with asthma, with higher rates for Hispanics (Puerto Rican) and African Americans. Familial history and infant mattress dust mite levels were positively associated with risk of asthma. In continuing to follow the population we will evaluate environmental risk factors for asthma development through age 7 and assess antigen specific IgE status of the children. In this application we are proposing to expand the prospective study to explore gene-environment interactions in the risk of asthma development. We aim to investigate the respective roles of allergens, ETS and other air contaminant exposures and, initially, one of several candidate genes - a polymorphism in the promoter region of the IL-4 gene, a gene found to be important for risk of atopy and asthma development. Blood samples will be banked so that, in the future, other candidate genes may be explored. Our extensive characterization of environmental exposures and risk factors provide a unique population within which gene-environment interactions in the development of asthma and atopy can be examined and may provide information necessary for targeting and prioritizing environmental interventions toward those with genetic susceptibility.