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!
Not of Divided Mind
19.01.2017 | Hertie-Institut für klinische Hirnforschung (HIH)
CRISPR meets single-cell sequencing in new screening method
19.01.2017 | CeMM Forschungszentrum für Molekulare Medizin der Österreichischen Akademie der Wissenschaften
An important step towards a completely new experimental access to quantum physics has been made at University of Konstanz. The team of scientists headed by...
Yersiniae cause severe intestinal infections. Studies using Yersinia pseudotuberculosis as a model organism aim to elucidate the infection mechanisms of these...
Researchers from the University of Hamburg in Germany, in collaboration with colleagues from the University of Aarhus in Denmark, have synthesized a new superconducting material by growing a few layers of an antiferromagnetic transition-metal chalcogenide on a bismuth-based topological insulator, both being non-superconducting materials.
While superconductivity and magnetism are generally believed to be mutually exclusive, surprisingly, in this new material, superconducting correlations...
Laser-driving of semimetals allows creating novel quasiparticle states within condensed matter systems and switching between different states on ultrafast time scales
Studying properties of fundamental particles in condensed matter systems is a promising approach to quantum field theory. Quasiparticles offer the opportunity...
Among the general public, solar thermal energy is currently associated with dark blue, rectangular collectors on building roofs. Technologies are needed for aesthetically high quality architecture which offer the architect more room for manoeuvre when it comes to low- and plus-energy buildings. With the “ArKol” project, researchers at Fraunhofer ISE together with partners are currently developing two façade collectors for solar thermal energy generation, which permit a high degree of design flexibility: a strip collector for opaque façade sections and a solar thermal blind for transparent sections. The current state of the two developments will be presented at the BAU 2017 trade fair.
As part of the “ArKol – development of architecturally highly integrated façade collectors with heat pipes” project, Fraunhofer ISE together with its partners...
19.01.2017 | Event News
10.01.2017 | Event News
09.01.2017 | Event News
19.01.2017 | Earth Sciences
19.01.2017 | Life Sciences
19.01.2017 | Physics and Astronomy