An international scientific team has discovered a gene associated with a high risk of severe childhood asthma. The specific gene variant may be an actual cause of this form of asthma, a leading cause of hospitalization in young children.
"Because asthma is a complex disease, with multiple interacting causes, we concentrated on a specific phenotype—severe, recurrent asthma occurring between ages two and six," said co-lead author of the study, Hakon Hakonarson, M.D., Ph.D., director of the Center for Applied Genomics at The Children's Hospital of Philadelphia (CHOP). "Identifying a risk susceptibility gene linked to this phenotype may lead to more effective, targeted treatments for this type of childhood asthma."
The study, published today in Nature Genetics, includes collaborators from centers in five countries. The corresponding author, Klaus Bonnelykke, M.D., Ph.D., is from the University of Copenhagen in Denmark. Hakonarson's collaborators from CHOP are Patrick Sleiman, Ph.D., and Michael March, Ph.D.
The study team performed a genome-wide association study (GWAS) on DNA from Danish national health registries and the Danish National Screening Biobank. In the discovery phase of their study, they compared genomes from 1,173 children aged 2 to 6 years from the Copenhagen Prospective Study on Asthma in Childhood (COSPAC) with genomes from 2,522 adult and pediatric control subjects without asthma.
In addition to finding further evidence for four genes previously implicated as asthma susceptibility genes, the researchers identified a novel gene, CDHR3, which is particularly active in epithelial cells lining the surfaces of airways. The study team then replicated their findings using data from other children of both European and non-European ancestry.
"Asthma researchers have been increasingly interested in the role of the airway epithelium in the development of asthma," said Hakonarson, a pediatric pulmonologist. "Abnormalities in the epithelial cells may increase a patient's risk to environmental triggers by exaggerating immune responses and making the airway overreact. Because the CDHR3 gene is related to a family of proteins involved in cell adhesion and cell-to-cell interaction, it is plausible that variations in this gene may disrupt normal functioning in these airway cells, and make a child vulnerable to asthma."
Hakonarson said that the current findings are consistent with previous investigations by CHOP's Center for Applied Genomics, suggesting that other genes linked to childhood asthma play a role in oversensitive immune reactions.
Hakonarson added that further studies are needed to better understand how the CDHR3 gene may function in asthma, with the eventual goal of using such knowledge to design better treatments for children with severe cases of this disease.
Support for this study came from the Danish Medical Research Council and an Institutional Development Fund grant from The Children's Hospital of Philadelphia.
"A genome-wide association study identifies CDHR3 as a susceptibility locus for early childhood asthma with severe exacerbations," Nature Genetics, published online Nov. 17, 2013. http://dx.doi.org/10.1038/ng.2830
About The Children's Hospital of Philadelphia: The Children's Hospital of Philadelphia was founded in 1855 as the nation's first pediatric hospital. Through its long-standing commitment to providing exceptional patient care, training new generations of pediatric healthcare professionals and pioneering major research initiatives, Children's Hospital has fostered many discoveries that have benefited children worldwide. Its pediatric research program receives the highest amount of National Institutes of Health funding among all U.S. children's hospitals. In addition, its unique family-centered care and public service programs have brought the 527-bed hospital recognition as a leading advocate for children and adolescents. For more information, visit http://www.chop.edu.
John Ascenzi | EurekAlert!
Scientists enlist engineered protein to battle the MERS virus
22.05.2017 | University of Toronto
Insight into enzyme's 3-D structure could cut biofuel costs
19.05.2017 | DOE/Los Alamos National Laboratory
Two-dimensional magnetic structures are regarded as a promising material for new types of data storage, since the magnetic properties of individual molecular building blocks can be investigated and modified. For the first time, researchers have now produced a wafer-thin ferrimagnet, in which molecules with different magnetic centers arrange themselves on a gold surface to form a checkerboard pattern. Scientists at the Swiss Nanoscience Institute at the University of Basel and the Paul Scherrer Institute published their findings in the journal Nature Communications.
Ferrimagnets are composed of two centers which are magnetized at different strengths and point in opposing directions. Two-dimensional, quasi-flat ferrimagnets...
An Australian-Chinese research team has created the world's thinnest hologram, paving the way towards the integration of 3D holography into everyday...
In the race to produce a quantum computer, a number of projects are seeking a way to create quantum bits -- or qubits -- that are stable, meaning they are not much affected by changes in their environment. This normally needs highly nonlinear non-dissipative elements capable of functioning at very low temperatures.
In pursuit of this goal, researchers at EPFL's Laboratory of Photonics and Quantum Measurements LPQM (STI/SB), have investigated a nonlinear graphene-based...
Dental plaque and the viscous brown slime in drainpipes are two familiar examples of bacterial biofilms. Removing such bacterial depositions from surfaces is...
For the first time, scientists have succeeded in studying the strength of hydrogen bonds in a single molecule using an atomic force microscope. Researchers from the University of Basel’s Swiss Nanoscience Institute network have reported the results in the journal Science Advances.
Hydrogen is the most common element in the universe and is an integral part of almost all organic compounds. Molecules and sections of macromolecules are...
22.05.2017 | Event News
17.05.2017 | Event News
16.05.2017 | Event News
22.05.2017 | Materials Sciences
22.05.2017 | Life Sciences
22.05.2017 | Physics and Astronomy