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Scientists Discover Genetic Profile of Chronic Allergic Disease of Children
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Scientists Discover Genetic Profile of Chronic Allergic Disease of Children

Scientists Discover Genetic Profile of Chronic Allergic Disease of Children
News

Scientists Discover Genetic Profile of Chronic Allergic Disease of Children

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Though many parents may never have heard of it, a severe and chronic condition called eosinophilic esophagitis (EE) is recognized by doctors as an emerging health problem for children.

Now, an interdisciplinary team of scientists funded in part by the National Institute of Allergy and Infectious Diseases (NIAID) and the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), both components of the National Institutes of Health (NIH), has published a major advance in understanding EE.

In the February 2006 issue of the "Journal of Clinical Investigation", the team reveals that a highly specific subset of human genes plays a role in this complicated disease.

"Understanding the genetic profile of a disease such as EE is an important first step towards developing new ways to diagnose and treat it," says NIAID Director Anthony S. Fauci, M.D.

At the Cincinnati Children's Hospital Medical Center, Professor of Pediatrics Marc E. Rothenberg, M.D., Ph.D., has seen patients with EE for a number of years and pursued clinical and laboratory research on the disease as well.

To better understand the disease, Dr. Rothenberg and his colleagues examined the gene expression in tissue samples taken directly from the esophagus of individuals with EE as well as from people without the disease.

These individuals were selected to represent a diverse sample with respect to age, sex and disease state. Dr. Rothenberg and his colleagues found that a particular set of 574 genes were expressed differently in people with EE from people without the illness.

This transcript signature, as they call it, yielded some surprising findings; it was largely the same for every person with EE, regardless of age and whether or not these people had food allergies.

This transcript signature was quite distinct from the signature observed in patients with acid reflux disease, thus allowing the two diseases to be easily discriminated.

Although EE is more common in males than in females, the genes expressed in the esophagus did not vary dramatically between males and females with EE.

Of the 574 genes, the investigators found that the expression of one gene in particular, termed "eotaxin-3", was elevated in people with EE compared to people without the disease - at up to 100-fold greater amounts in EE than controls.

"Eotaxin-3", a factor released from certain cells and tissues, acts to attract circulating eosinophils, yet no one had previously observed that the local levels of "eotaxin-3" correlated directly with the number of eosinophils in the esophagus.

In their paper, Dr. Rothenberg and his colleagues also demonstrated that, in a mouse model of EE, mice lacking receptors for eotaxin were protected against developing EE.

These results, when taken with those of the human studies, suggest that a drug to block "eotaxin-3" might have therapeutic value.

Finally, by sequencing the "eotaxin-3" genes of all the people in their study, the investigators identified certain genetic variations known as single nucleotide polymorphisms - particular spots within the DNA sequence of the gene where a single base of DNA may vary from person to person.

One particular SNP in the gene appears to occur more frequently in patients with EE than in controls, and, if this is confirmed, SNPs may provide a way to determine if people are at risk for EE.

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