28 Nov Genetics Plays Large Role in Allergic Esophagitis
MedicalResearch.com Interview with:
Dr. Hakon Hakonarson MD PhD
The Center for Applied Genomics, The Children’s Hospital of Philadelphia
Department of Pediatrics, The Perelman School of Medicine,
University of Pennsylvania Philadelphia, Philadelphia, Pennsylvania
Medical Research: What is the background for this study? What are the main findings?
Dr. Hakonarson: We have built the world’s largest pediatric biobank at the Center for Applied Genomics at CHOP. Eosinophilic esophagitis (EoE) is among the projects we have sampled in collaboration with the EoE Center in collaboration with Dr. Spergel. We have nearly 1,000 samples now of this relatively rare disorder, which is now well powered for GWAS. We previously reported association of the TSLP locus with Eosinophilic esophagitis. Here we report genome-wide significant associations at four additional loci; c11orf30 and STAT6, which have been previously associated with both atopic and autoimmune diseases, and two EoE-specific loci, ANKRD27 that regulates the trafficking of melanogenic enzymes to epidermal melanocytes and CAPN14, that encodes a calpain whose expression is highly enriched in the esophagus in EoE. This discovery not only improves our understanding of the pathobiology of EoE, but also represents novel targets for the development of new therapies to treat the disease.
Medical Research: What should clinicians and patients take away from your report?
Dr. Hakonarson: That EoE is a complex genetic disorder that is highly heritable and as we learn more about the genetic underpinnings of EoE we will be able to develop more innovative and effective therapies to treat EoE.
Medical Research: What recommendations do you have for future research as a result of this study?
Dr. Hakonarson: The results from this study inform us that genetics plays a key role in the pathogenesis of Eosinophilic esophagitis. By future sequencing of EoE samples, we will be able to explain the major genetic factors and gene networks that cause EoE and develop more effective therapies and preventive measures to treat this devastating disease.
GWAS identifies four novel eosinophilic esophagitis loci
Patrick M. A. Sleiman,Mei-Lun Wang, Antonella Cianferoni,Seema Aceves,Nirmala Gonsalves, Kari Nadeau, Albert J. Bredenoord, Glenn T. Furuta, Jonathan M. Spergel,Hakon Hakonarson
Nature Communications 5, Article number: 5593 doi:10.1038/ncomms659