Asthma and allergies are the most common chronic diseases of childhood, and their prevalence in Western countries continues to increase. Asthma and other allergic diseases are complex diseases, and environmental exposures, likely interacting with genetic risk factors, play important roles in the development of these disorders. Recent studies have shown that exposure to animals early in life may protect against asthma and allergies, and it is thought that endotoxin exposure mediates this effect. Endotoxin is comprised of soluble lipopolysaccharide (LPS) fragments of the outer membrane of gram-negative bacteria. It is postulated that endotoxin exposure may prevent the development of asthma and allergic disease depending on dose, timing, and genetics of the individual. Endotoxin is first sensed and recognized by components of the innate immune system, which then sets off a cascade of reactions, culminating in production of cytokines and co-stimulatory molecules which may be important in directing the development of the adaptive immune system. This application seeks to examine whether genes encoding components of the innate immune system are associated with the development of asthma and allergies, and whether endotoxin interacts with these genes in the development of these disorders. The research design will be a candidate gene case-control study, and gene-by-environment interactions will be tested. This application will combine resources and data from two birth cohorts: the Boston Home Allergens and Asthma Study and the Connecticut Childhood Asthma Study. In doing so, we will increase the number of cases and controls, and will be able to make use of previously collected data and specimens. Blood for genetic material is currently being collected on the two cohorts, and endotoxin will be measured from stored, frozen house dust.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Project (R01)
Project #
5R01AI056230-03
Application #
7208966
Study Section
Epidemiology of Clinical Disorders and Aging Study Section (ECDA)
Program Officer
Togias, Alkis
Project Start
2005-06-15
Project End
2010-02-28
Budget Start
2007-03-01
Budget End
2008-02-29
Support Year
3
Fiscal Year
2007
Total Cost
$600,696
Indirect Cost
Name
Brigham and Women's Hospital
Department
Type
DUNS #
030811269
City
Boston
State
MA
Country
United States
Zip Code
02115
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