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Scientists deepen genetic understanding of eosinophilic esophagitis


Scientists funded by the National Institutes of Health (NIH) have identified genetic markers associated with eosinophilic esophagitis (EoE), an inflammatory disease characterized by high levels of immune cells called eosinophils in the esophagus. Their findings suggest that several genes are involved in the development of EoE, which can cause difficulty eating and often is associated with food allergies. The findings also may help explain why the disease specifically affects the esophagus. The work was supported in part by the Consortium of Food Allergy Research, which is funded by NIH's National Institute of Allergy and Infectious Diseases and National Institute of Diabetes and Digestive and Kidney Diseases.

A team led by researchers at Cincinnati Children's Hospital Medical Center searched the entire human genome for variations between 9,246 healthy people and 736 people with EoE. They confirmed previous results from a smaller study that linked variations in the region on chromosome 5 containing TSLP, a gene associated with allergic diseases, to a higher risk of developing EoE. They also identified variations in a region on chromosome 2 containing a gene called CAPN14, which produces an enzyme called calpain 14, that are associated with higher EoE risk. The researchers showed that CAPN14 is expressed, or "turned on," primarily in the esophagus. CAPN14 expression and calpain activity rose when scientists treated cultured esophageal cells with a molecule that induces allergic inflammation, suggesting that the enzyme is part of an anti-inflammatory response. People with EoE who carry the variant form of the gene may be unable to mount this response as effectively.

Further research is needed to determine if these findings might lead to identification of biomarkers to detect a person's risk of developing EoE. Understanding the factors underlying EoE may help guide development of new diagnostic and treatment strategies for the disease.


Contact: Hillary Hoffman
NIH/National Institute of Allergy and Infectious Diseases

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