PMID- 32798708
OWN - NLM
STAT- MEDLINE
DCOM- 20211004
LR  - 20220531
IS  - 1542-7714 (Electronic)
IS  - 1542-3565 (Linking)
VI  - 19
IP  - 10
DP  - 2021 Oct
TI  - STAT6 Variants Associate With Relapse of Eosinophilic Esophagitis in Patients 
      Receiving Long-term Proton Pump Inhibitor Therapy.
PG  - 2046-2053.e2
LID - S1542-3565(20)31129-0 [pii]
LID - 10.1016/j.cgh.2020.08.020 [doi]
AB  - 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 (r(2) >/=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.
CI  - Copyright (c) 2021 The Authors. Published by Elsevier Inc. All rights reserved.
FAU - Mougey, Edward B
AU  - Mougey EB
AD  - Center for Pharmacogenomics and Translational Research, Nemours Children's Health 
      System, Jacksonville, Florida.
FAU - Nguyen, Vivian
AU  - Nguyen V
AD  - College of Pharmacy, University of Florida, Jacksonville, Florida.
FAU - Gutierrez-Junquera, Carolina
AU  - Gutierrez-Junquera C
AD  - Pediatric Gastroenterology Unit.
FAU - Fernandez-Fernandez, Sonia
AU  - Fernandez-Fernandez S
AD  - Pediatric Gastroenterology Unit.
FAU - Cilleruelo, Maria Luz
AU  - Cilleruelo ML
AD  - Pediatric Gastroenterology Unit.
FAU - Rayo, Ana
AU  - Rayo A
AD  - Pediatric Gastroenterology Unit.
FAU - Borrell, Belen
AU  - Borrell B
AD  - Pediatric Gastroenterology Unit.
FAU - Roman, Enriqueta
AU  - Roman E
AD  - Pediatric Gastroenterology Unit.
FAU - Gonzalez-Lois, Carmen
AU  - Gonzalez-Lois C
AD  - Department of Pathology, Hospital Universitario Puerta de Hierro-Majadahonda, 
      Autonomous University of Madrid, Madrid, Spain.
FAU - Chao, Montserrat
AU  - Chao M
AD  - Department of Pathology, Hospital Universitario Severo Ochoa, Leganes, Madrid, 
      Spain.
FAU - Al-Atrash, Hadeel
AU  - Al-Atrash H
AD  - 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.
FAU - Franciosi, James P
AU  - Franciosi JP
AD  - 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: 
      James.Franciosi@Nemours.org.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20200813
PL  - United States
TA  - Clin Gastroenterol Hepatol
JT  - Clinical gastroenterology and hepatology : the official clinical practice journal 
      of the American Gastroenterological Association
JID - 101160775
RN  - 0 (Proton Pump Inhibitors)
RN  - 0 (STAT6 Transcription Factor)
RN  - 0 (STAT6 protein, human)
SB  - IM
MH  - Adolescent
MH  - Child
MH  - Child, Preschool
MH  - *Eosinophilic Esophagitis/drug therapy/genetics
MH  - Humans
MH  - Longitudinal Studies
MH  - Prospective Studies
MH  - *Proton Pump Inhibitors/therapeutic use
MH  - Recurrence
MH  - STAT6 Transcription Factor/genetics
OTO - NOTNLM
OT  - Biomarker
OT  - Esophagus
OT  - Immune Response
OT  - Response to Treatment
EDAT- 2020/08/18 06:00
MHDA- 2021/10/05 06:00
CRDT- 2020/08/18 06:00
PHST- 2020/02/17 00:00 [received]
PHST- 2020/07/06 00:00 [revised]
PHST- 2020/08/09 00:00 [accepted]
PHST- 2020/08/18 06:00 [pubmed]
PHST- 2021/10/05 06:00 [medline]
PHST- 2020/08/18 06:00 [entrez]
AID - S1542-3565(20)31129-0 [pii]
AID - 10.1016/j.cgh.2020.08.020 [doi]
PST - ppublish
SO  - Clin Gastroenterol Hepatol. 2021 Oct;19(10):2046-2053.e2. doi: 
      10.1016/j.cgh.2020.08.020. Epub 2020 Aug 13.