Summary

Asthma is an epidemic that disproportionately affects children, the poor and certain racial/ethnic groups. Latinos/Hispanics are the fastest growing minority population in the US and are disproportionately affected by asthma morbidity. From 1990 to 2000 there was an 81% increase in number of people that mark their ethnic origin as Peruvian on the US Census survey and the prevalence of asthma in Peru is among one of the highest in the world. Asthma is a complex disease and genetic risk for asthma and asthma morbidity may be modified by environmental exposures. The indoor environment is of particular concern as most people spend the majority of their time indoors. Investigators in this application have shown that high levels of indoor exposures, including particulate matter (PM) and nitrogen dioxide (NO2), are independently associated with greater asthma morbidity, and are particularly high in Peruvian homes. The burden of asthma attributable to differences in domestic PM and NO2 concentrations is substantial; however, not all children are susceptible to effects of pollutant exposure and a large variation in response exists between individuals. These findings suggest a strong possibility of an interaction between genetic predisposition and environmental exposure in the development of asthma. To address the critical questions of the role of genetic susceptibility to the adverse effects of indoor air pollution on asthma, we will build upon the infrastructure and ongoing data collection efforts in Peru. We propose a candidate gene study to identify genetic variants associated with asthma and its associated traits (i.e., asthma severity, pulmonary function, airway inflammation) in relation to indoor air pollutant exposure in two Peruvian cities, Lima and Tumbes. We will prioritize candidate genes identified by published genome-wide association studies for asthma as well as those in the oxidative stress pathway thought to be relevant to pollutant exposure and asthma. We will cross-validate associations identified in well characterized asthma cases and controls from Lima, Peru (n=1,400), in a second independent population of asthmatic cases and controls recruited from Tumbes, Peru (n=400). Specific Aim #1: To identify genes associated with asthma in children in Peru. Specific Aim #2: To determine if genetic risk for asthma is modified by indoor air pollutant (PM, NO2) concentrations. We anticipate identifying candidate genes for asthma and associated traits relevant to both the general population as well as those contributing to disparities in asthma morbidity among individuals in Peru. Identifying subgroups of the population who are particularly vulnerable to air pollution is an important objective, as the results can be used to identify people most likely to benefit from exposure avoidance.