This project describes the role of the lab of Stephanie London in the Laboratory of Respiratory Biology in support of her epidemiologic studies. The laboratory is engaged in selection of polymorphisms for analysis, using bioinformatic methods and genotyping analysis of samples from Dr. London's epidemiologic studies of respiratory disease. In the past year, we have focused on the study of childhood asthma in Mexico City (described under project entitled Genetic And Environmental Factors In Childhood Respiratory Health). The laboratory uses primarily real-time PCR technology to identify genetic polymorphisms in these samples. DIR has recently acquired an Illumina reader. Our lab staff have been trained on the use of this technology and we are planning our first set of genotyping using this technology. The lab staff have also received additional offsite training in haplotype analysis and bioinformatics in service of the labs goals. ? ? We are developing plans to collaborate with David Schwartz's group to analyze the Mexico City study for genes involved in innate immunity (1,536 SNPs using an Illumina panel). This work will be done jointly with Huiling Li and the staff of the Schwartz lab using the new core Illumina facility. This panel will also be examined in other studies in the Schwartz lab enabling comparison data. We are collaborating with statistical geneticist Dimitri Zaykin to use Bayesian methods for analyses of these data when they are available to deal with the multiple comparison issue in a manner that maximizes prior information about the genes and SNPs in this panel. ? ? In the coming year, we expect to receive samples from asthma cases and controls in the Singapore Chinese Cohort study. We will then examine candidate genes that are relevant to the cohort exposures in addition to genes that we are examining in the Mexico study. This will enable confirmation of findings across multiple populations.

Agency
National Institute of Health (NIH)
Institute
National Institute of Environmental Health Sciences (NIEHS)
Type
Intramural Research (Z01)
Project #
1Z01ES025045-07
Application #
7327306
Study Section
Project Start
Project End
Budget Start
Budget End
Support Year
7
Fiscal Year
2006
Total Cost
Indirect Cost
Name
U.S. National Inst of Environ Hlth Scis
Department
Type
DUNS #
City
State
Country
United States
Zip Code
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
London, Stephanie J (2007) Gene-air pollution interactions in asthma. Proc Am Thorac Soc 4:217-20
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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