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 Southern California, Wuhan China and Mexico City and the study of nonmalignant respiratory disease is in Singapore. These international populations are of interest because rates of asthma vary widely. 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. We have nominated genes for screening for polymorphisms through the Environmental Genome Project. Once these candidate genes be screened, we would follow-up any polymorphisms in the epidemiologic studies as well as screening for functional significance. This past year has been devoted to setting up the laboratory and hiring/training a technician and postdoc. We have done this with the help of Doug Bell. We have completed laboratory analysis of three polymorphisms involved in DNA repair in the lung cancer study - two in the XRCC1 gene and one in the XPD gene. We will be examining additional lung cancer candidate genes. With respect to asthma, we are currently establishing assays for two polymorphisms recently described in the IL-13 gene which appear to influence function. One is in the promoter region at -1055 and one in the coding region (exon 4) leads to an amino acid substitution (Arg 130Gln). We will be pursuing additional candidate genes for asthma in this next year. In addition to asthma candidates based on previous linkage results, we are interested in examining polymorphisms in the Tlr4 gene that appear to involved in response to endotoxin, ozone and particles , an exposure which is high for both the Mexico City and Wuhan studies, and for the Mexico City study, ozone. Mexico City has the highest ozone levels in North America. The laboratory techniques involved include RFLP/PCR and TaqMan PCR.

National Institute of Health (NIH)
National Institute of Environmental Health Sciences (NIEHS)
Intramural Research (Z01)
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U.S. National Inst of Environ Hlth Scis
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House, John S; Li, Huiling; DeGraff, Laura M et al. (2015) Genetic variation in HTR4 and lung function: GWAS follow-up in mouse. FASEB J 29:323-35
Reddy, Poovendhree; Naidoo, Rajen N; Robins, Thomas G et al. (2012) GSTM1 and GSTP1 gene variants and the effect of air pollutants on lung function measures in South African children. Am J Ind Med 55:1078-86
London, Stephanie J; Romieu, Isabelle (2009) Gene by environment interaction in asthma. Annu Rev Public Health 30:55-80
Li, Huiling; Romieu, Isabelle; Wu, Hao et al. (2007) Genetic polymorphisms in transforming growth factor beta-1 (TGFB1) and childhood asthma and atopy. Hum Genet 121:529-38
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Wu, Hao; Romieu, Isabelle; Sienra-Monge, Juan-Jose et al. (2007) Genetic variation in S-nitrosoglutathione reductase (GSNOR) and childhood asthma. J Allergy Clin Immunol 120:322-8
Wu, Hao; Romieu, Isabelle; Sienra-Monge, Juan-Jose et al. (2007) Parental smoking modifies the relation between genetic variation in tumor necrosis factor-alpha (TNF) and childhood asthma. Environ Health Perspect 115:616-22
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Romieu, I; Sienra-Monge, J J; Ramirez-Aguilar, M et al. (2004) Genetic polymorphism of GSTM1 and antioxidant supplementation influence lung function in relation to ozone exposure in asthmatic children in Mexico City. Thorax 59:8-10
David, Gloria L; Romieu, Isabelle; Sienra-Monge, Juan Jose et al. (2003) Nicotinamide adenine dinucleotide (phosphate) reduced:quinone oxidoreductase and glutathione S-transferase M1 polymorphisms and childhood asthma. Am J Respir Crit Care Med 168:1199-204

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