2000 Progress Report: Genetic Mechanisms of Susceptibility to Inhaled Pollutants
EPA Grant Number: R826724C003Subproject: this is subproject number 003 , established and managed by the Center Director under grant R826724
(EPA does not fund or establish subprojects; EPA awards and manages the overall grant for this center).
Center: CECEHDPR - Johns Hopkins University Hospital
Center Director: Eggleston, Peyton A.
Title: Genetic Mechanisms of Susceptibility to Inhaled Pollutants
Investigators: Kleeberger, Steven R.
Institution: Johns Hopkins University
EPA Project Officer: Fields, Nigel
Project Period: January 1, 1998 through January 1, 2002
Project Period Covered by this Report: January 1, 1999 through January 1, 2000
Project Amount: Refer to main center abstract for funding details.
RFA: Centers for Children's Environmental Health and Disease Prevention Research (1998)
Research Category: Health Effects , Children's Health
Description:
Objective:This research project will examine the genetic basis for susceptibility to an inflammatory response in airways to reactive oxidant species generated as a result of exposure to ozone. Ozone has been linked to respiratory morbidity in population studies, and it is also apparent that there is marked inter-individual variation in response to ozone exposure in adults and children. Using mouse strains with known susceptibility O3 induced airway inflammation, this project will generate high-resolution linkage maps of the regions of mouse chromosomes 17 and 11 carrying O3 susceptibility loci. Later, we will use comparative mapping approaches to search for homologous human susceptibility loci. We will develop congenic strains of mice that contain the genomic regions that confer differential genetic susceptibility to inflammatory response and epithelial injury. Finally, we will characterize the kinetics of the response to O3 in resistant and -susceptible congenic mouse strains to evaluate the mechanisms through which the susceptibility locus modulates susceptibility. In as much as there is close linkage homology between mouse and human genomes, the identification of genes that control susceptibility to O3 in this model may provide a means to characterize individuals in human populations who are at risk to oxidant exposures. The community-based studies in this Center will seek to relate ozone exposure to asthma morbidity, and will have developed relationship with families of asthmatic children in the community to allow us to plan genetic studies of pollutant response. Progress Summary:
This research project examined the genetic basis for susceptibility to an inflammatory response in airways to reactive oxidant species generated as a result of exposure to ozone. Ozone has been linked to respiratory morbidity in population studies, and it is also apparent that there is marked inter-individual variation in response to ozone exposure in adults and children. Using mouse strains with known susceptibility O3 induced airway inflammation, this project will generate high-resolution linkage maps of the regions of mouse chromosomes 17 and 11 carrying O3 susceptibility loci. The investigators are using comparative mapping approaches to search for homologous human susceptibility loci. They will develop congenic strains of mice that contain the genomic regions that confer differential genetic susceptibility to inflammatory response and epithelial injury. Finally, they will characterize the kinetics of the response to O3 in resistant and -susceptible congenic mouse strains to evaluate the mechanisms through which the susceptibility locus modulates susceptibility. In as much as there is close linkage homology between mouse and human genomes, the identification of genes that control susceptibility to O3 in this model may provide a means to characterize individuals in human populations who are at risk to oxidant exposures. The community-based studies in this Center will seek to relate ozone exposure to asthma morbidity, and will have developed relationship with families of asthmatic children in the community to allow researchers to plan genetic studies of pollutant response. Future Activities:
This research project will continue to examine the genetic basis for susceptibility to an inflammatory response in airways to reactive oxidant species generated as a result of exposure to ozone. Ozone has been linked to respiratory morbidity in population studies, and it is also apparent that there is marked inter-individual variation in response to ozone exposure in adults and children. Using mouse strains with known susceptibility O3 induced airway inflammation, this project will generate high-resolution linkage maps of the regions of mouse chromosomes 17 and 11 carrying O3 susceptibility loci. Later, the investigators will use comparative mapping approaches to search for homologous human susceptibility loci. They will develop congenic strains of mice that contain the genomic regions that confer differential genetic susceptibility to inflammatory response and epithelial injury. Finally, they will characterize the kinetics of the response toO3in resistant and -susceptible congenic mouse strains to evaluate the mechanisms through which the susceptibility locus modulates susceptibility. In as much as there is close linkage homology between mouse and human genomes, the identification of genes that control susceptibility toO3 in this model may provide a means to characterize individuals in human populations who are at risk to oxidant exposures. The community-based studies in this Center will seek to relate ozone exposure to asthma morbidity, and will have developed relationship with families of asthmatic children in the community to allow researchers to plan genetic studies of pollutant response. Supplemental Keywords:
Health, RFA, Scientific Discipline, Allergens/Asthma, Atmospheric Sciences, Biochemistry, Children's Health, Disease & Cumulative Effects, Ecological Risk Assessment, Epidemiology, Health Risk Assessment, Risk Assessments, Human Health Risk Assessment, age-related differences, air pollutants, air pollution, air toxics, airborne pollutants, airborne urban contaminants, airway disease, airway inflammation, ambient particulates, asthma, asthma morbidity, asthmatic children, children, children's environmental health, community based, community-based intervention, disease, environmental health, epidemelogy, epidemeology, health effects, human exposure, human health risk, morbidity , Air, Scientific Discipline, Health, RFA, Susceptibility/Sensitive Population/Genetic Susceptibility, Biology, Risk Assessments, genetic susceptability, Health Risk Assessment, Chemistry, Children's Health, particulate matter, Environmental Chemistry, Allergens/Asthma, Genetics, environmental hazard exposures, allergen, health effects, inhalation, allergens, air quality, ozone, ozone induced airway dysfunction, assessment of exposure, childhood respiratory disease, environmental health effects, susceptibility, toxics, community-based intervention, human health effects, particulates, respiratory, sensitive populations, biological response, genetic mechanisms, air pollution, airway disease, children, inhaled, cellular biology, analytical chemistry, community-based studies, disease, exposure, airway epithelial cells, environmental health hazard, asthma, genetic predisposition, human exposure, Human Health Risk Assessment, morbidity, PM, airway inflammation, community based
Relevant Websites:
"A Randomized, Controlled Trial of Home Exposure Control in Asthma"
http://cfpub.epa.gov/ncer_abstracts/index.cfm/fuseaction/display.abstractDetail/abstract/1081
"Mechanisms Of Particulate-Induced Allergic Asthma"
http://cfpub.epa.gov/ncer_abstracts/index.cfm/fuseaction/display.abstractDetail/abstract/1082
"Genetic Mechanisms of Susceptibility to Inhaled Pollutants"
http://cfpub.epa.gov/ncer_abstracts/index.cfm/fuseaction/display.abstractDetail/abstract/1083
Progress and Final Reports:
Original Abstract
2002 Progress Report
Main Center Abstract and Reports:
R826724 CECEHDPR - Johns Hopkins University Hospital
Subprojects under this Center: (EPA does not fund or establish subprojects; EPA awards and manages the overall grant for this center).
R826724C001 A Randomized, Controlled Trial of Home Exposure Control in Asthma
R826724C002 Mechanisms Of Particulate-Induced Allergic Asthma
R826724C003 Genetic Mechanisms of Susceptibility to Inhaled Pollutants
R826724C004 The Relationship Of Airborne Pollutants And Allergens To Asthma Morbidity