PMID- 34337835
OWN - NLM
STAT- MEDLINE
DCOM- 20220316
LR  - 20230701
IS  - 1365-2982 (Electronic)
IS  - 1350-1925 (Print)
IS  - 1350-1925 (Linking)
VI  - 34
IP  - 1
DP  - 2022 Jan
TI  - Pharmacogenomics fail to explain proton pump inhibitor refractory esophagitis in 
      pediatric esophageal atresia.
PG  - e14217
LID - 10.1111/nmo.14217 [doi]
AB  - BACKGROUND: Esophagitis is prevalent in patients with esophageal dysmotility 
      despite acid suppression, likely related to poor esophageal clearance. Esophageal 
      atresia (EA) is a classic model of dysmotility where this observation holds true. 
      In adult non-dysmotility populations, failure of esophagitis to respond to proton 
      pump inhibitors (PPI) has been linked to variants in CYP2C19 that influence the 
      activity of the encoded enzyme. It is unknown if CYP2C19 metabolizer phenotype 
      contributes to PPI-refractory, non-allergic esophagitis in EA. METHODS: We 
      performed a cross-sectional study of 314 children with (N = 188) and without 
      (N = 126) EA who were on PPI therapy at the time of endoscopy to evaluate for 
      possible gastroesophageal reflux disease. Patients with eosinophilic esophagitis 
      and/or fundoplication were excluded. Clinical and histology data were collected. 
      Genomic DNA from biopsy samples was genotyped for polymorphisms in CYP2C19. 
      RESULTS: CYP2C19 metabolizer phenotypes were not associated with presence or 
      severity of esophagitis (P = 0.994). In a multivariate logistic regression 
      adjusted for potential confounders, EA was the strongest and only significant 
      predictor of esophagitis (odds ratio 2.72, P = 0.023). Using negative binomial 
      regression, we found that CYP2C19 phenotype was not a significant predictor of 
      eosinophil count in children with PPI-refractory esophagitis. CONCLUSIONS: 
      Patients with EA are significantly more likely to experience PPI-refractory, 
      non-allergic esophagitis than controls regardless of CYP2C19 metabolizer 
      phenotype, suggesting that factors other than CYP2C19 genetics, including 
      dysmotility, are the primary drivers of esophagitis in EA. CYP2C19 genotype 
      failed to predict PPI-refractory, non-allergic esophagitis in both EA and non-EA 
      children.
CI  - (c) 2021 John Wiley & Sons Ltd.
FAU - Yasuda, Jessica L
AU  - Yasuda JL
AUID- ORCID: 0000-0002-4998-3322
AD  - Division of Gastroenterology, Hepatology and Nutrition, Boston Children's 
      Hospital, Boston, MA, USA.
FAU - Staffa, Steven J
AU  - Staffa SJ
AD  - Department of Anesthesiology, Critical Care, and Pain Medicine, Boston Children's 
      Hospital, Boston, MA, USA.
FAU - Nurko, Samuel
AU  - Nurko S
AUID- ORCID: 0000-0003-0936-4807
AD  - Division of Gastroenterology, Hepatology and Nutrition, Boston Children's 
      Hospital, Boston, MA, USA.
FAU - Kane, Madeline
AU  - Kane M
AD  - Division of Gastroenterology, Hepatology and Nutrition, Boston Children's 
      Hospital, Boston, MA, USA.
FAU - Wall, Stephanie
AU  - Wall S
AD  - Division of Gastroenterology, Hepatology and Nutrition, Boston Children's 
      Hospital, Boston, MA, USA.
FAU - Mougey, Edward B
AU  - Mougey EB
AD  - Center for Pharmacogenomics and Translational Research, Nemours Children's Health 
      System, Jacksonville, FL, USA.
FAU - Franciosi, James P
AU  - Franciosi JP
AD  - Division of Gastroenterology, Hepatology, and Nutrition, Nemours Children's 
      Hospital, Orlando, FL, USA.
AD  - Department of Pediatrics, University of Central Florida College of Medicine, 
      Orlando, FL, USA.
FAU - Manfredi, Michael A
AU  - Manfredi MA
AD  - Division of Gastroenterology, Hepatology and Nutrition, Boston Children's 
      Hospital, Boston, MA, USA.
FAU - Rosen, Rachel
AU  - Rosen R
AUID- ORCID: 0000-0003-3949-3060
AD  - Division of Gastroenterology, Hepatology and Nutrition, Boston Children's 
      Hospital, Boston, MA, USA.
LA  - eng
GR  - R01 DK097112/DK/NIDDK NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
DEP - 20210801
PL  - England
TA  - Neurogastroenterol Motil
JT  - Neurogastroenterology and motility
JID - 9432572
RN  - 0 (Proton Pump Inhibitors)
RN  - EC 1.14.14.1 (Cytochrome P-450 CYP2C19)
SB  - IM
MH  - Child, Preschool
MH  - Cross-Sectional Studies
MH  - Cytochrome P-450 CYP2C19/*genetics
MH  - Esophageal Atresia/complications/*drug therapy/genetics
MH  - Esophagitis/*drug therapy/etiology/genetics
MH  - Female
MH  - Genotype
MH  - Humans
MH  - Infant
MH  - Male
MH  - Pharmacogenetics
MH  - Proton Pump Inhibitors/*therapeutic use
PMC - PMC10302247
MID - NIHMS1839029
OTO - NOTNLM
OT  - CYP2C19
OT  - dysmotility
OT  - esophageal atresia
OT  - esophagitis
OT  - proton pump inhibitor metabolism
EDAT- 2021/08/03 06:00
MHDA- 2022/03/17 06:00
PMCR- 2023/06/28
CRDT- 2021/08/02 06:31
PHST- 2021/06/01 00:00 [revised]
PHST- 2020/12/22 00:00 [received]
PHST- 2021/06/07 00:00 [accepted]
PHST- 2021/08/03 06:00 [pubmed]
PHST- 2022/03/17 06:00 [medline]
PHST- 2021/08/02 06:31 [entrez]
PHST- 2023/06/28 00:00 [pmc-release]
AID - 10.1111/nmo.14217 [doi]
PST - ppublish
SO  - Neurogastroenterol Motil. 2022 Jan;34(1):e14217. doi: 10.1111/nmo.14217. Epub 
      2021 Aug 1.