After performing a genome-wide association study, the study team found EoE was linked to a region of chromosome 5 that includes two genes. The likely culprit is the gene TSLP, which has higher activity levels in children with EoE compared to healthy subjects. In addition, TSLP has been previously linked to allergic inflammatory diseases, such as asthma and the skin inflammation, atopic dermatitis.
"This gene is a plausible candidate because of its biological role in allergic inflammation," said study leader Hakon Hakonarson, M.D., Ph.D., director of the Center for Applied Genomics at The Children's Hospital of Philadelphia. Hakonarson and colleagues collaborated with Marc E. Rothenberg, M.D., Ph.D., director of the Center for Eosinophilic Disorders at the Cincinnati Children's Hospital Medical Center.
The study appears online today in Nature Genetics.
Only recently recognized as a distinct condition, EoE, like other allergies, has been increasing over the past 20 years, and its reported incidence of one in 10,000 people may be an underestimate. The hallmark of EoE is swelling and inflammation in the esophagus, accompanied by high levels of immune cells called eosinophils. It can affect people of any age, but is more common among young men who have a history of other allergic diseases such as asthma and eczema. EoE is often first discovered in children with feeding difficulties and failure to thrive.
In the current study, the researchers performed a genome-wide analysis on 181 samples from the Cincinnati center, compared to nearly 2,000 healthy controls from The Children's Hospital of Philadelphia (CHOP). They then replicated the initial findings with additional DNA samples from EoE patients and controls at CHOP. The gene studies pointed to chromosome 5q22.1, which contains the TSLP gene. TLSP holds the genetic code to produce a cytokine, a specific signaling protein that regulates inflammatory responses occurring in allergic diseases.
Because children with EoE are often allergic to many foods, they may be limited to an elemental formula containing no large food proteins, to allow time for their symptoms to resolve. Physicians then perform tests to determine which foods a child can or cannot eat.
"Eosinophilic esophagitis is a highly allergic disease, and one that is rapidly expanding," said allergist Jonathan M. Spergel, M.D., a co-first author of the study, who sees large numbers of patients with EoE as director of the Center for Pediatric Eosinophilic Disorders at The Children's Hospital of Philadelphia. "This is the first genome-wide association study done on this disease, and now that we have elucidated a gene pathway, the hope is that physicians can eventually intervene in that pathway and discover a new treatment."
The National Institutes of Health provided funding support for this study, along with the Food Allergy Project, the Campaign Urging Research for Eosinophilic Disorders (CURED) Foundation, the American Partnership for Eosinophilic Disorders (APFED), The Children's Hospital of Philadelphia Chair's Institute, the Buckeye Foundation, and the Cotswold Foundation.
"Common variants at 5q22 associate with pediatric eosinophilic esophagitis," Nature Genetics, published online March 7, 2010. http://dx.doi.org/10.1038/ng.547
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 is among the largest in the country, ranking second in National Institutes of Health funding. In addition, its unique family-centered care and public service programs have brought the 441-bed hospital recognition as a leading advocate for children and adolescents.
John Ascenzi | EurekAlert!
Discovery of a Key Regulatory Gene in Cardiac Valve Formation
24.05.2017 | Universität Basel
Carcinogenic soot particles from GDI engines
24.05.2017 | Empa - Eidgenössische Materialprüfungs- und Forschungsanstalt
Physicists from the University of Würzburg are capable of generating identical looking single light particles at the push of a button. Two new studies now demonstrate the potential this method holds.
The quantum computer has fuelled the imagination of scientists for decades: It is based on fundamentally different phenomena than a conventional computer....
An international team of physicists has monitored the scattering behaviour of electrons in a non-conducting material in real-time. Their insights could be beneficial for radiotherapy.
We can refer to electrons in non-conducting materials as ‘sluggish’. Typically, they remain fixed in a location, deep inside an atomic composite. It is hence...
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...
24.05.2017 | Event News
23.05.2017 | Event News
22.05.2017 | Event News
24.05.2017 | Physics and Astronomy
24.05.2017 | Physics and Astronomy
24.05.2017 | Event News