Genetic Mechanisms of Susceptibility to Inhaled Pollutants

EPA Grant Number: R826724C003
Subproject: 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. , Eggleston, Peyton A.
Current Investigators: Kleeberger, Steven R.
Institution: The Johns Hopkins University
EPA Project Officer: Callan, Richard
Project Period: January 1, 1998 through January 1, 2002
Project Amount: Refer to main center abstract for funding details.
RFA: Centers for Children's Environmental Health and Disease Prevention Research (1998) RFA Text |  Recipients Lists
Research Category: Children's Health , Health Effects , Health

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 to 03 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 genornic regions that confer differential genetic susceptibility to inflammatory response and epithelial injury. Finally, we will characterize the kinetics of the response toO3 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 toO3in 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.

Supplemental Keywords:

children, health, asthma, exposure, ozone, genetic risk., RFA, Health, Scientific Discipline, Air, particulate matter, Genetics, Environmental Chemistry, Health Risk Assessment, Chemistry, Risk Assessments, Susceptibility/Sensitive Population/Genetic Susceptibility, Allergens/Asthma, Children's Health, genetic susceptability, Biology, asthma, health effects, particulates, sensitive populations, airway epithelial cells, community-based intervention, morbidity, human health effects, inhaled pollutants, cellular biology, airway disease, biological response, ozone, exposure, genetic predisposition, air pollution, airway inflammation, children, community based, Human Health Risk Assessment, ozone induced airway dysfunction, genetic mechanisms, environmental health effects, inhalation, assessment of exposure, childhood respiratory disease, susceptibility, community-based studies, human exposure, analytical chemistry, environmental health hazard, inhaled, PM, allergens, allergen, disease, respiratory, air quality, environmental hazard exposures

Progress and Final Reports:

2000 Progress Report
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