Pharmacogenomic predictors of proton pump inhibitor response in pediatric eosinophilic esophagitis
Abstract
BackgroundGenetic variability has been implicated in the heterogeneous response to proton pump inhibitors (PPIs) in eosinophilic esophagitis (EoE), with variants in CYP2C19 and STAT6 previously associated with treatment outcome. However, the broader pharmacogenomic determinants underlying interindividual variability in PPI response remain incompletely understood.MethodsThis study aimed to investigate whether genetic variability in Absorption, Distribution, Metabolism, and Excretion (ADME) genes contributes to PPI response in pediatric EoE. Fifty-eight patients (17 responders, PPI-RE, and 41 non-responders, PPI-NORE) were genotyped using the Drug Metabolizing Enzymes and Transporters (DMET) Plus microarray, covering 231 ADME-related genes. Genetic and clinical data were integrated using a machine learning–based approach to explore determinants of treatment response.ResultsCHST3 rs4148944 G/G genotype showed the strongest nominal association with PPI response (p < 0.0064). Integrative analysis revealed combinatorial patterns involving CHST3, CHST11 gene (rs7847), SULT1A2/A3 (rs11859842), and NR1I3 (rs55802895), particularly in the presence of food allergy, which improved patient stratification. Although these additional variants were not individually significant, their combined occurrence—especially in association with food allergy—suggests a potential contribution of both metabolic and regulatory pathways to PPI response variability.ConclusionOverall, this study provides exploratory, proof-of-concept evidence that the CHST3 rs4148944 G/G genotype, together with other genetic variants and clinical features, may influence PPI response in EoE and contribute to patient stratification. These findings support the potential of integrative pharmacogenomic approaches, although validation in larger cohorts is required.
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BibTeX
@article{arbitrio2026pharmacogenomic,
title = {{Pharmacogenomic predictors of proton pump inhibitor response in pediatric eosinophilic esophagitis}},
author = {Mariamena Arbitrio and Renato Tambucci and Valeria Tallarico and Ilaria Gnasso and Francesca Scionti and Giuseppe Agapito and Emanuela Altomare and Mario Cannataro and Graziella D'Arrigo and Giovanni Tripepi and Daniela Concolino and Fabiola De Masi and Maria Giovanna Puoti and Francesca Rea and Monica Malamisura and Alessandra Maria Ricci and Maria Cristina Artesani and Sara Urbani and Veronica Calandrelli and Alessandro Giovanni Fiocchi and Paola De Angelis and Licia Pensabene},
journal = {Frontiers in Pharmacology},
year = {2026},
month = oct,
doi = {10.3389/fphar.2026.1913372},
url = {https://www.frontiersin.org/articles/10.3389/fphar.2026.1913372},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Pharmacogenomic predictors of proton pump inhibitor response in pediatric eosinophilic esophagitis
AU - Mariamena Arbitrio
AU - Renato Tambucci
AU - Valeria Tallarico
AU - Ilaria Gnasso
AU - Francesca Scionti
AU - Giuseppe Agapito
AU - Emanuela Altomare
AU - Mario Cannataro
AU - Graziella D'Arrigo
AU - Giovanni Tripepi
AU - Daniela Concolino
AU - Fabiola De Masi
AU - Maria Giovanna Puoti
AU - Francesca Rea
AU - Monica Malamisura
AU - Alessandra Maria Ricci
AU - Maria Cristina Artesani
AU - Sara Urbani
AU - Veronica Calandrelli
AU - Alessandro Giovanni Fiocchi
AU - Paola De Angelis
AU - Licia Pensabene
PY - 2026
DA - 2026/10/30
JO - Frontiers in Pharmacology
DO - 10.3389/fphar.2026.1913372
UR - https://www.frontiersin.org/articles/10.3389/fphar.2026.1913372
AB - BackgroundGenetic variability has been implicated in the heterogeneous response to proton pump inhibitors (PPIs) in eosinophilic esophagitis (EoE), with variants in CYP2C19 and STAT6 previously associated with treatment outcome. However, the broader pharmacogenomic determinants underlying interindividual variability in PPI response remain incompletely understood.MethodsThis study aimed to investigate whether genetic variability in Absorption, Distribution, Metabolism, and Excretion (ADME) genes contributes to PPI response in pediatric EoE. Fifty-eight patients (17 responders, PPI-RE, and 41 non-responders, PPI-NORE) were genotyped using the Drug Metabolizing Enzymes and Transporters (DMET) Plus microarray, covering 231 ADME-related genes. Genetic and clinical data were integrated using a machine learning–based approach to explore determinants of treatment response.ResultsCHST3 rs4148944 G/G genotype showed the strongest nominal association with PPI response (p < 0.0064). Integrative analysis revealed combinatorial patterns involving CHST3, CHST11 gene (rs7847), SULT1A2/A3 (rs11859842), and NR1I3 (rs55802895), particularly in the presence of food allergy, which improved patient stratification. Although these additional variants were not individually significant, their combined occurrence—especially in association with food allergy—suggests a potential contribution of both metabolic and regulatory pathways to PPI response variability.ConclusionOverall, this study provides exploratory, proof-of-concept evidence that the CHST3 rs4148944 G/G genotype, together with other genetic variants and clinical features, may influence PPI response in EoE and contribute to patient stratification. These findings support the potential of integrative pharmacogenomic approaches, although validation in larger cohorts is required.
SN - 1663-9812
ER -