STAT6 variants associate with relapse of fosinophilic esophagitis in patients receiving long-term proton pump inhibitor therapy
Entity
UAM. Departamento de Anatomía Patológica; UAM. Departamento de PediatríaPublisher
Elsevier, Inc.Date
2021-10-01Citation
10.1016/j.cgh.2020.08.020
Clinical Gastroenterology and Hepatology 19.10 (2020): 2046-2053
ISSN
1542-3565DOI
10.1016/j.cgh.2020.08.020Editor's Version
https://doi.org/10.1016/j.cgh.2020.08.020Subjects
Biomarker; Esophagus; Immune Response; Response to Treatment; MedicinaRights
© 2020 by the AGA Institute.Esta obra está bajo una licencia de Creative Commons Reconocimiento-NoComercial-SinObraDerivada 4.0 Internacional.
Abstract
Background & Aims: 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. Methods: 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. Results: 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. Conclusions: 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.
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Google Scholar:Mougey, Edward B.
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Nguyen, Vivian
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Gutiérrez Junquera, Carolina
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Fernández-Fernández, Sonia
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Cilleruelo, Maria Luz
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Rayo, Ana
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Borrell, Belén
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Román Riechmann, Enriqueta
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González-Lois, Carmen
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Chao, Montserrat
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Al-Atrash, Hadeel
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Franciosi, James P.
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