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Association Between CYP2C19*17 Alleles and pH Probe Testing Outcomes in Children With Symptomatic Gastroesophageal

James P Franciosi1, Edward B Mougey2, Andre Williams3

  • 1Division of Gastroenterology, Nemours Children's Hospital, Orlando, FL, USA.

Journal of Clinical Pharmacology
|September 9, 2017
PubMed

Insights

Proton pump inhibitor (PPI) dosing for pediatric gastroesophageal reflux disease (GERD) may be improved by considering CYP2C19 genetic variants. Children with CYP2C19*17 alleles showed increased acid exposure, suggesting genotype-guided dosing is needed.

Area of Science:

  • Pharmacogenomics
  • Pediatric Gastroenterology
  • Gastrointestinal Motility

Background:

  • Esophageal pH monitoring is key for diagnosing gastroesophageal reflux disease (GERD).
  • Proton pump inhibitor (PPI) resistance in GERD may link to CYP2C19 genetic variations.
  • Current pediatric PPI dosing ignores CYP2C19 variants, potentially causing underdosing and misinterpreting treatment failure.

Purpose of the Study:

  • To investigate the association between CYP2C19*17 alleles and esophageal acid exposure outcomes in children with suspected GERD undergoing pH testing.
  • To determine if CYP2C19 genetic variants influence PPI efficacy in pediatric GERD patients.

Main Methods:

  • Retrospective cohort study of 74 children (0.71-17.1 years) with stored tissue samples and prior esophageal pH testing on PPI therapy.
  • Genotyping for common CYP2C19 alleles, categorizing participants into CYP2C19*17 carriers (cases) versus controls.
  • Analysis of pH probe acid exposure metrics (time and percentage with pH < 4) in relation to CYP2C19*17 allelic status, controlling for confounders.

Main Results:

  • Children carrying CYP2C19*17 alleles without loss-of-function variants showed significantly longer times (76.46 vs 33.47 min, P=.03) and higher percentage of time (5.71 vs 2.67 min, P=.04) with esophageal pH < 4 compared to controls.
  • These associations remained significant after adjusting for test duration, PPI dose, and race in multiple-regression models.
  • Findings suggest CYP2C19*17 allele carriers experience greater acid exposure despite PPI therapy.

Conclusions:

  • The CYP2C19*17 allele is associated with increased esophageal acid exposure in children with GERD symptoms on PPI therapy.
  • Current PPI dosing strategies may be suboptimal for pediatric GERD patients with specific CYP2C19 genotypes.
  • Genotype-guided PPI dosing before esophageal pH testing could optimize treatment for children carrying CYP2C19*17 alleles.

Keywords:
CYP2C19GERDchildrenproton pump inhibitor

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