Accession Number : ADA567625


Title :   Genetics of Eosinophilic Esophagitis


Descriptive Note : Final rept. 1 Mar 2010-29 Feb 2012


Corporate Author : CHILDREN'S HOSPITAL MEDICAL CENTER CINCINNATI OH


Personal Author(s) : Rothenberg, Marc


Full Text : https://apps.dtic.mil/dtic/tr/fulltext/u2/a567625.pdf


Report Date : Mar 2012


Pagination or Media Count : 36


Abstract : Eosinophilic esophagitis (EE) is an emerging worldwide food allergic disorder associated with polysensitization to multiple food allergens, resulting in greatly restricted diets and chronic gastroesophageal reflux disease-like symptoms in many individuals. EE has a strong genetic component based on the frequent presence of a familial inheritance pattern, the high sibling risk ratio (80-fold) and the demonstration that a single nucleotide polymorphism (SNP) in the eotaxin-3 gene confers disease susceptibility. In order to dissect disease pathogenesis in humans, we are now taking genetic approaches based on genome-wide expression profile analysis of esophageal tissue, as well as a genomic analysis based on a candidate gene approach. The central hypothesis of our grant is that EE has strong genetic components that can be elucidated by a candidate gene approach focused on genes involved in asthma, allergy, and celiac disease. Using this approach, our preliminary studies have led us to hypothesize that EE susceptibility involves the IL-2/IL-21 genetic locus, a region known to be involved in immune-mediated diseases, especially autoimmunity. We have been pursuing candidate gene validation (Aim 1) and biological assessment of one lead candidate, IL-21 (Aim 2). We have identified preliminary genetic susceptibility loci involved in EE, which has led us to the identification of key potential pathogenic steps involving TSLP, IL21, and TGFb.


Descriptors :   *EOSINOPHILS , *ESOPHAGUS , *GENETICS , ALLERGIC DISEASES , FOOD , INFLAMMATION , ORDER DISORDER TRANSFORMATIONS


Subject Categories : Genetic Engineering and Molecular Biology
      Anatomy and Physiology
      Medicine and Medical Research


Distribution Statement : APPROVED FOR PUBLIC RELEASE