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
Araki, Tetsuro; Nishino, Mizuki; Gao, Wei et al. (2016) Normal thymus in adults: appearance on CT and associations with age, sex, BMI and smoking. Eur Radiol 26:15-24
Araki, Tetsuro; Nishino, Mizuki; Gao, Wei et al. (2015) Pulmonary cysts identified on chest CT: are they part of aging change or of clinical significance? Thorax 70:1156-62
Araki, Tetsuro; Nishino, Mizuki; Zazueta, Oscar E et al. (2015) Paraseptal emphysema: Prevalence and distribution on CT and association with interstitial lung abnormalities. Eur J Radiol 84:1413-8
Araki, Tetsuro; Nishino, Mizuki; Gao, Wei et al. (2015) Anterior Mediastinal Masses in the Framingham Heart Study: Prevalence and CT Image Characteristics. Eur J Radiol Open 2:26-31
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
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
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
Nakahira, Kiichi; Kyung, Sun-Young; Rogers, Angela J et al. (2013) Circulating mitochondrial DNA in patients in the ICU as a marker of mortality: derivation and validation. PLoS Med 10:e1001577; discussion e1001577
Hunninghake, Gary M; Hatabu, Hiroto; Okajima, Yuka et al. (2013) MUC5B promoter polymorphism and interstitial lung abnormalities. N Engl J Med 368:2192-200

Showing the most recent 10 out of 31 publications