This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. ABSTRACT Background Asthma is caused by the interaction of genetic and environmental factors. In the U.S., asthma prevalence, morbidity and mortality are highest in Puerto Ricans, intermediate in Dominicans and Cubans, and lowest in Mexicans and Central Americans. Latinos are admixed and share varying proportions of African, Native American and European ancestry. The mixed ancestry of Latinos provides unique opportunities in epidemiological and genetic studies of complex traits and may be useful in untangling complex gene-environment (G x E) interactions in disease susceptibility. Purpose and Objectives We will collect a well-characterized sample of Latino individuals with asthma (n = 2000) and clinic-based controls (n = 2000), age 8-21 years, from the Bronx, NY, Chicago, IL, San Francisco, CA, Houston, TX, and Puerto Rico 1) Test the hypothesis that genetic ancestry interacts with environmental/demographic risk factors to modify asthma risk and asthma-related phenotypes. 2) Genotype fifty candidate genes that may be involved in G x E interactions relevant to asthma. 3) Determine whether migration and acculturation are associated with asthma and severe asthma. Design Case control study with the objective of collecting a well-characterized sample of Latino asthmatics (n = 2000) and clinic-based controls (n = 2000), age 8-21 years, from the Bronx, NY, Chicago, IL, San Francisco, CA, Houston, TX and Puerto Rico. The Houston site will be responsible for recruiting and enrolling 400 cases and 400 control subjects over a 3 year period. The genetics laboratory will be at University of California, San Francisco Inclusion Criteria: Procedures Study procedures include 1) Completion of questionnaire instrument (by parent if 18 years) 2. Spirometry with bronchodilator challenge (cases only) 3. Obtain blood specimen. Blood cells may be cryopreserved and immortalized. 4. Perform skin prick testing using Multi-Test II devices and standardized, commercially available extracts to determine cutaneous reactions to common aero-allergens. 5. If 12% improvement in FEV1 demonstrated on bronchodilator challenge testing, CASES ONLY will be eligible for methacholine challenge testing to confirm the diagnosis of asthma. Methacholine challenge tests will require a second visit. I. HYPOTHESIS 1) We will test the hypothesis that genetic ancestry interacts with environmental/demographic risk factors to modify asthma risk and asthma-related phenotypes in Latinos of high risk Puerto Rican, intermediate risk Dominican, and low risk Central American and Mexican ethnicities. 2) We will genotype fifty candidate genes that may be involved in G x E interactions relevant to asthma. We will test whether there are ethnic-specific G x E interactions that differentially affect asthma risk, severity and pharmacologic response among Latino ethnic groups. 3) We will determine whether migration and acculturation are associated with asthma and severe asthma. II.
SPECIFIC AIMS We will collect a well-characterized sample of Latino individuals with asthma (n = 2000) and clinic-based controls (n = 2000), age 8-21 years, from the Bronx, NY, Chicago, IL, San Francisco, CA, Houston, TX, and Puerto Rico from which the specific hypotheses described above can be tested. The Houston site will be responsible for recruiting 400 cases and 400 controls over a 3 year period.
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