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STAT6 Variants Associate With Relapse of Eosinophilic Esophagitis in Patients Receiving Long-term Proton Pump Inhibitor Therapy.

Authors
  • Mougey, Edward B1
  • Nguyen, Vivian2
  • Gutiérrez-Junquera, Carolina3
  • Fernández-Fernández, Sonia3
  • Cilleruelo, Maria Luz3
  • Rayo, Ana3
  • Borrell, Belén3
  • Román, Enriqueta3
  • González-Lois, Carmen4
  • Chao, Montserrat5
  • Al-Atrash, Hadeel6
  • Franciosi, James P7
  • 1 Center for Pharmacogenomics and Translational Research, Nemours Children's Health System, Jacksonville, Florida.
  • 2 College of Pharmacy, University of Florida, Jacksonville, Florida.
  • 3 Pediatric Gastroenterology Unit.
  • 4 Department of Pathology, Hospital Universitario Puerta de Hierro-Majadahonda, Autonomous University of Madrid, Madrid, Spain. , (Spain)
  • 5 Department of Pathology, Hospital Universitario Severo Ochoa, Leganés, Madrid, Spain. , (Spain)
  • 6 Division of Gastroenterology, Hepatology and Nutrition, Nemours Children's Health System, Orlando, Florida; Department of Pediatrics, University of Central Florida College of Medicine, Orlando, Florida.
  • 7 Division of Gastroenterology, Hepatology and Nutrition, Nemours Children's Health System, Orlando, Florida; Department of Pediatrics, University of Central Florida College of Medicine, Orlando, Florida. Electronic address: [email protected]
Type
Published Article
Journal
Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association
Publication Date
Oct 01, 2021
Volume
19
Issue
10
Identifiers
DOI: 10.1016/j.cgh.2020.08.020
PMID: 32798708
Source
Medline
Keywords
Language
English
License
Unknown

Abstract

Based on histologic features, variants in STAT6 are associated with a poor initial response to proton pump inhibitor (PPI) therapy in pediatric patients with eosinophilic esophagitis (EoE). We investigated whether these genetic variants are associated with a poor long-term response in children with EoE who initially responded to PPI therapy. We performed a prospective longitudinal cohort study of children ages 2 to 16 years who met the diagnostic criteria for EoE (≥15 eosinophils/high-power field [eos/hpf]), responded to 8 weeks of treatment with 2 mg/kg/d PPI (<15 eos/hpf), and whose dose then was reduced to 1 mg/kg/d PPI (maintenance therapy) for 1 year, at which point biopsy specimens were collected by endoscopy. Genomic DNA was isolated from formalin-fixed paraffin-embedded biopsy tissue and was genotyped for variants of STAT6. Remission of inflammation was assessed at eos/hpf thresholds of <15 and ≤5. Among 73 patients who received 1 mg/kg/d PPI maintenance therapy for 1 year, 13 patients (18%) had 6 to 14 eos/hpf, 36 patients (49%) had 5 or fewer eos/hpf, and 24 patients (33%) relapsed to EoE (≥15 eos/hpf). Carriage of any of 3 STAT6 variants in linkage disequilibrium (r2 ≥0.8; rs324011, rs167769, or rs12368672) was associated with a 2.3- to 2.8-fold increase in the odds of EoE relapse, and with a 2.8- to 4.1-fold increase in the odds of having 6 to 14 eos/hpf. For rs324011, the odds ratio [95% CI] for relapse was 2.77 [1.11, 6.92]; P = .029, and the odds ratio [95% CI] for having 6 to 14 eos/hpf was 3.06 [1.27, 7.36]; P = .012. Pediatric EoE patients who initially respond to PPI therapy and carry STAT6 variants rs324011, rs167769, or rs12368672 are at increased risk of relapse after 1 year of PPI maintenance therapy. Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.

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