March 8, 2010
Gene Site Found For Children’s Food Allergy
Gene linked to eosinophilic esophagitis plays key role in inflammation
Pediatrics researchers have identified the first major gene location responsible for a severe, often painful type of food allergy called eosinophilic esophagitis (EoE). In this disease, which may cause weight loss, vomiting, heartburn and swallowing difficulties, a patient may be unable to eat a wide variety of foods.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.
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