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. 2022 Jan;34(1):e14217.
doi: 10.1111/nmo.14217. Epub 2021 Aug 1.

Pharmacogenomics fail to explain proton pump inhibitor refractory esophagitis in pediatric esophageal atresia

Jessica L Yasuda  1 , Steven J Staffa  2 , Samuel Nurko  1 , Madeline Kane  1 , Stephanie Wall  1 , Edward B Mougey  3 , James P Franciosi  4   5 , Michael A Manfredi  1 , Rachel Rosen  1
Affiliations

Pharmacogenomics fail to explain proton pump inhibitor refractory esophagitis in pediatric esophageal atresia

Jessica L Yasuda et al. Neurogastroenterol Motil. 2022 Jan.

Abstract

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.

Keywords: CYP2C19; dysmotility; esophageal atresia; esophagitis; proton pump inhibitor metabolism.

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Figures

FIGURE 1
FIGURE 1
Diagram detailing datasets and excluded patients for EA cases (A) and non-EA controls (B)
FIGURE 2
FIGURE 2
Distributions of CYP2C19 metabolizer phenotypes among sub-populations with and without esophagitis expressed as a percentage of the total at-risk patients. A. Entire cohort. B. EA subgroup. C. non-EA subgroup
FIGURE 3
FIGURE 3
Distributions of STAT6 rs324011 genotypes among sub-populations with and without esophagitis expressed as a percentage of the total at-risk patients. A. Entire cohort. B. EA subgroup. C. non-EA subgroup
See this image and copyright information in PMC

References

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