This project provides genetic analyses for epidemiologic studies being conducted by Stephanie London through the epidemiology branch. The epidemiologic projects are referenced described under the following Z01 project numbers - 49017, 49019, 43012. In brief, these are epidemiology studies of lung cancer (49017), childhood respiratory illness (49019, including asthma and impaired lung function) and adult nonmalignant respiratory illness (43012). These studies are being conducted in various ethnic groups. The studies of lung cancer are in African-Americans, Caucasians, and Shanghai, Chinese. The studies of childhood respiratory illness include populations in Wuhan China and Mexico City and the study of nonmalignant respiratory disease is in Singapore. We are pursuing a candidate gene approach selecting polymorphisms in genes with potential relevance to asthma based on their function and, in some instances additional their location in regions of linkage for asthma. The emphasis is on functionally significant polymorphisms. In the past year, we have focused our work on candidate genes studies of asthma in the study of Mexico City children. The laboratory techniques involved include RFLP/PCR, ARMS-PRC, and TaqMan PCR. In the upcoming year, we will focus our attention on the study of candidate genes for asthma in Mexico City children. This population is of great interest because exposure to ozone are the highest in North America. Ozone has been linked to asthma exacerbations but the relation with incidence has been more difficult to prove. Some recent data suggests that ozone may indeed cause asthma. However, it is clear from chamber studies that individuals vary widely in their susceptibility to ozone. It is likely that a large part of this susceptibility is genetic. Linkage studies in mice provide evidence for a specific genetic variation in susceptibility to respiratory effects of ozone. The ability to distinguish susceptible subpopulations would increase the power of epidemiologic studies to determin respiratory effects of ozone. In the past year, we have published three papers resulting from work in this newly established laboratory. We have two papers on polymorphisms in DNA repair genes and lung cancer -- XRCC1, XPD, and XRCC3. We have also published a paper demonstrating the efficacy of a method that we developed for collection of a large quantity of DNA from buccal cells in school children. In the past year, we have concentrated our efforts on studying candidate genes of asthma in the Mexico City study. We are focusing on asthma candidate genes that are plausibly involved in respiratory response to ozone. In addition to candidate genes chosen by mechanistic considerations, we are also pursuing candidate genes that arise from quantitative trait linkage studies of respiratory responses to ozone relevant to asthma in mouse models. In the past year, we have examined polymorphisms in the following genes -- tlr4, myeloperoxidase, MnSOD, IL-6, IL-8, IL-13, tnf-alpha, GSTM1, and lactoferrin. We are currently examining GSTP1 and NQ01.
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