Although asthma is a significant public health problem among Hispanics in the United States and in Latin America, little is known about the contribution of genetic factors to the pathogenesis of asthma in this ethnic group. We have previously identified significant evidence of linkage to total serum IgE on chromosome 20p12 among males in a genetically isolated Hispanic population in Costa Rica. This proposal seeks to identify genetic determinants of total serum IgE - a critical intermediate phenotype of asthma- on chromosome 20p12. We will first conduct a fine-mapping association analysis of total serum IgE on chromosome 20p12 in Costa Rican boys with asthma and their parents. We will then attempt to replicate positive findings among families of white (non-Hispanic) boys in the Childhood Asthma Management Program (CAMP). After identification of a susceptibility gene(s) for total IgE in males, we will assess the generalizability of our findings by performing association studies of newly identified candidate genes among families of girls with asthma in both Costa Rica and CAMP. Finally, we will assess the expression of these candidate genes on CD4+ T lymphocytes and examine whether selected variants affect gene expression signatures for total serum IgE among children with asthma in CAMP. This proposal offers a unique opportunity to identify an asthma-susceptibility gene(s) in general and among Hispanics in particular. STATEMENT ON

Public Health Relevance

Little is known about the genetics of asthma in Hispanics, despite the disproportionate burden of asthma in certain Hispanic subgroups in both the U.S. and in Latin America. This proposal will utilize state-of-the-art genetic and genomic approaches to help to understand a component of the genetic regulation of total serum IgE, a critical intermediate of asthma, in general and among Hispanics in particular.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Clinical Investigator Award (CIA) (K08)
Project #
5K08HL092222-05
Application #
8309041
Study Section
Special Emphasis Panel (ZHL1-CSR-N (F1))
Program Officer
Tigno, Xenia
Project Start
2008-07-01
Project End
2014-06-30
Budget Start
2012-07-01
Budget End
2014-06-30
Support Year
5
Fiscal Year
2012
Total Cost
$138,780
Indirect Cost
$10,280
Name
Brigham and Women's Hospital
Department
Type
DUNS #
030811269
City
Boston
State
MA
Country
United States
Zip Code
02115
Doyle, Tracy J; Dellaripa, Paul F; Batra, Kerri et al. (2014) Functional impact of a spectrum of interstitial lung abnormalities in rheumatoid arthritis. Chest 146:41-50
Putman, Rachel K; Rosas, Ivan O; Hunninghake, Gary M (2014) Genetics and early detection in idiopathic pulmonary fibrosis. Am J Respir Crit Care Med 189:770-8
Rogers, Angela J; McGeachie, Michael; Baron, Rebecca M et al. (2014) Metabolomic derangements are associated with mortality in critically ill adult patients. PLoS One 9:e87538
Mihalek, Andrew D; Rosas, Ivan O; Padera Jr, Robert F et al. (2013) Interstitial pneumonitis and the risk of chronic allograft rejection in lung transplant recipients. Chest 143:1430-5
Hunninghake, Gary M; Hatabu, Hiroto; Okajima, Yuka et al. (2013) MUC5B promoter polymorphism and interstitial lung abnormalities. N Engl J Med 368:2192-200
Granada, Mark; Wilk, Jemma B; Tuzova, Marina et al. (2012) A genome-wide association study of plasma total IgE concentrations in the Framingham Heart Study. J Allergy Clin Immunol 129:840-845.e21
Doyle, Tracy J; Hunninghake, Gary M; Rosas, Ivan O (2012) Subclinical interstitial lung disease: why you should care. Am J Respir Crit Care Med 185:1147-53
Doyle, Tracy J; Washko, George R; Fernandez, Isis E et al. (2012) Interstitial lung abnormalities and reduced exercise capacity. Am J Respir Crit Care Med 185:756-62
Xu, Jin-Fu; Washko, George R; Nakahira, Kiichi et al. (2012) Statins and pulmonary fibrosis: the potential role of NLRP3 inflammasome activation. Am J Respir Crit Care Med 185:547-56
Sharma, Sunita; Murphy, Amy; Howrylak, Judie et al. (2011) The impact of self-identified race on epidemiologic studies of gene expression. Genet Epidemiol 35:93-101

Showing the most recent 10 out of 24 publications