How to Identify Gene-Modifiable Environment Risk Factors for Eosinophilic Esophagitis
MARCH 06, 2018
W. Todd Penberthy
Elizabeth T. Jensen, PhWhile advances have been made in understanding eosinophilic esophagitis (EoE), most studies have been descriptive and our understanding of the etiology of EoE remains elusive, according to researchers presenting at the 2018 American Academy of Allergy, Asthma & Immunology (AAAAI) and World Allergy Joint Congress in Orlando, FL.
Elizabeth T. Jensen, PhD, Assistant Professor in the Epidemiology & Prevention Center for Public Health Genomics at Wake Forest School of Medicine, told attendants of her lecture that she tries to frame research questions not just on determining disease mechanism, but on identifying opportunities for disease prevention and mitigation.
This, she explained, could be done through identification of “modifiable risk factors by consequential epidemiology.”
While it is unknown whether genetics, or environment, or both contribute to the occurrence of allergic diseases like EoE, examinations of EoE in monozygotic versus dizygotic twins does indicate that as much as 10% of the microbiome variability can be explained as due to variations in host genetics, Jensen said.
Jensen described the origins of the esophageal microbiome and how this may exert significant influences on EoE susceptibility against particular genetic backgrounds. She described 1 asthma outcome study where investigators clustered subjects by distinct microbiomes. These studies showed that the increased risk of asthma at age 5 due to changes in the microbiome at age 1 were only observable when the mother had asthma, thus showing a strong genetic component influencing the microbiome’s activity on asthma susceptibility.
She stressed that this supports that genetics can modify the susceptibilities we are observing.
In Jensen’s most recent case-controlled study on EoE, investigators examined 5 EoE-predisposing polymorphisms against early-life factors (antibiotic use in infancy, cesarean delivery, breast-feeding, neonatal intensive care unit admission, and absence of pets in the home) in hospital-based cases (n=127) against control subjects in the catchment area (n=121).
The most striking result that emerged was that breast-feeding decreased the susceptibility phenotype in women with CAPN14 genetic susceptibility by 92%, thus suggesting that EoE disease risk might be modifiable in subjects with certain gene variants.
This was a relatively small study, so Jensen plans to conduct larger analysis going forwards.
Jensen pointed out that there is a paucity of evidence assessing gene-environment microbiome interactions, and that much greater research attention should be devoted to consideration of genetic susceptibility. She stressed that more longitudinal EoE studies with greater consideration of the microbiome are need.
Jensen suggested there may be important, modifiable factor for stopping the increase of EoE prevalence that have not even been considered yet. But the increase in proton pump inhibitor drugs over the past 30 years does correlate with increases in EoE. Moreover, it may be actually be a particular combination of factors that is leading to EoE.
When asked whether there are other factors that can affect the esophageal microbiome, Jensen said that it is too early to say about the esophageal microbiome. Most microbiota studies have focused more on the gut.
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