Environment is key to understanding eosinophilic esophagitis

Published Online: September 22, 2014

Eosinophilic esophagitis (EoE) is an increasingly common inflammatory condition of the esophagus, likely involving both genetic and environmental causes. EoE researchers have identified genes that are associated with EoE such as CAPN14, TSLP, TSLPR, CCL26, and FLG. Although EoE clusters in families, genes do not tell the whole story. Prior studies found that environmental exposures, including antibiotics in the first year of life, may increase risk for EoE. Recently, it was reported that epigenetic mechanisms may “turn on” the eotaxin promoter, causing eosinophilic inflammation in the esophagus. New research recently published in The Journal of Allergy & Clinical Immunology (JACI) from the laboratory of Marc Rothenberg, MD, PhD and lead by Eileen Alexander, PhD at Cincinnati Children’s Hospital Medical Center reveals that environment plays a stronger role in pathogenesis than previously thought.

This new research study compared twins and nuclear families to estimate the contributions of genes and environment to EoE risk in susceptible families. A group of nuclear families at the Cincinnati Center for Eosinophilic Disorders (CCED) and also a new international registry of twins with EoE were established. Alexander and colleagues found that 1.8% of first-degree relatives and 2.4% of siblings also had EoE. Heritability appeared to be very high in the nuclear families (72.0%). However, when they analyzed both identical and fraternal twins with EoE, they were able to separate the effects of shared genes from common household environment. Common family environment accounted for 81%, whereas genes accounted for 15%. Early environmental risk factors included food allergies, high twin birth-weight difference, and self-reported penicillin allergy. Interestingly, fall birth season and breastfeeding may be protective.

When families affected by EoE ask, “Will my next child have EoE?” clinicians can state with confidence, “The risk of having a second child with EoE is about two-and-a-half percent.” This helps parents understand and plan for their families. The authors have shown that EoE clusters in families and have opened a new area of research, focusing on modifiable environmental factors that create risk in individuals and families with EoE. The twin and extended family registry will focus new research on both environmental and genetic causes of “complex” diseases, like EoE, especially in early life. The authors expect this will empower families and their physicians to recognize and make changes that reduce risk in genetically susceptible families.

The Journal of Allergy and Clinical Immunology (JACI) is an official scientific journal of the AAAAI, and is the most-cited journal in the field of allergy and clinical immunology.

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