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.

National Institute of Health (NIH)
National Institute of Allergy and Infectious Diseases (NIAID)
Research Project (R01)
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Epidemiology of Clinical Disorders and Aging Study Section (ECDA)
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Togias, Alkis
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Brigham and Women's Hospital
United States
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Sordillo, Joanne E; Kelly, Roxanne; Bunyavanich, Supinda et al. (2015) Genome-wide expression profiles identify potential targets for gene-environment interactions in asthma severity. J Allergy Clin Immunol 136:885-92.e2
Litonjua, Augusto A (2012) Vitamin D deficiency as a risk factor for childhood allergic disease and asthma. Curr Opin Allergy Clin Immunol 12:179-85
Sharma, Sunita; Poon, Audrey; Himes, Blanca E et al. (2012) Association of variants in innate immune genes with asthma and eczema. Pediatr Allergy Immunol 23:315-23
Lange, Nancy E; Zhou, Xiaobo; Lasky-Su, Jessica et al. (2011) Comprehensive genetic assessment of a functional TLR9 promoter polymorphism: no replicable association with asthma or asthma-related phenotypes. BMC Med Genet 12:26
Sordillo, Joanne E; Sharma, Sunita; Poon, Audrey et al. (2011) Effects of endotoxin exposure on childhood asthma risk are modified by a genetic polymorphism in ACAA1. BMC Med Genet 12:158
Wu, Ann Chen; Lasky-Su, Jessica; Rogers, Christine A et al. (2010) Fungal exposure modulates the effect of polymorphisms of chitinases on emergency department visits and hospitalizations. Am J Respir Crit Care Med 182:884-9
Wu, Ann Chen; Lasky-Su, Jessica; Rogers, Christine A et al. (2010) Polymorphisms of chitinases are not associated with asthma. J Allergy Clin Immunol 125:754-7, 757.e1-757.e2
Litonjua, Augusto A (2008) Dietary factors and the development of asthma. Immunol Allergy Clin North Am 28:603-29, ix