ArticleEuropean journal of pediatrics2018
Association between CYP2C19 extensive metabolizer phenotype and childhood anti-reflux surgery following failed proton pump inhibitor medication treatment.
Article in European journal of pediatrics, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers, 2 of them syntheses that pooled it.
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Who cites it
16 citing papers in PubMed, 2 syntheses or guidelines pooled it, 27 citations in OpenAlex.
- Effects of CYP2C19 genetic polymorphisms on the cure rates ofFrontiers in pharmacology · 2022Pooled it
- Clinical Pharmacogenetics Implementation Consortium (CPIC) Guideline for CYP2C19 and Proton Pump Inhibitor Dosing.Clinical pharmacology and therapeutics · 2021Guideline
- Novel Implementation of Genotype-Guided Proton Pump Inhibitor Medication Therapy in Children: A Pilot, Randomized, Multisite Pragmatic Trial.Clinical and translational science · 2019Trial
- Rome V Pediatric Upper Gastrointestinal Disorders of Gut-Brain Interaction.Gastroenterology · 2026Review
- A Pharmacogenetics-Based Approach to Managing Gastroesophageal Reflux Disease: Current Perspectives and Future Steps.Pharmacogenomics and personalized medicine · 2023Review
- Pharmacogenomics fail to explain proton pump inhibitor refractory esophagitis in pediatric esophageal atresia.Neurogastroenterology and motility · 2022Article
- Omeprazole Treatment Failure in Gastroesophageal Reflux Disease and Genetic Variation at theFrontiers in genetics · 2022Article
- Use of Pharmacogenomics to Guide Proton Pump Inhibitor Therapy in Clinical Practice.Digestive diseases and sciences · 2021Review
- Gene-Based Dose Optimization in Children.Annual review of pharmacology and toxicology · 2020Review
- Development and validation of T-ARMS-PCR to detect CYP2C19*17 allele.Journal of clinical laboratory analysis · 2020Article
- Article
- CYP2C19 and STAT6 Variants Influence the Outcome of Proton Pump Inhibitor Therapy in Pediatric Eosinophilic Esophagitis.Journal of pediatric gastroenterology and nutrition · 2019Article
- Genotype tailored treatment of mild symptomatic acid reflux in children with uncontrolled asthma (GenARA): Rationale and methods.Contemporary clinical trials · 2019Article
- Article
- Proton pump inhibitors: from CYP2C19 pharmacogenetics to precision medicine.Expert opinion on drug metabolism & toxicology · 2018Review
- From bench to bedside: a spotlight on pharmacogenomics at Nemours Children's Health.PharmacogenomicsArticle
Corrections and comments
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Authors and funding
9 authors at 6 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
When pediatric gastroesophageal reflux disease (GERD) that is refractory to proton pump inhibitor (PPI) medication treatment is identified in clinical practice and anti-reflux surgery (ARS) is being considered, genetic factors related to PPI metabolism by the CYP2C19 enzyme are currently not part of the clinical decision-making process. Our objective was to test the hypothesis that the distribution of the extensive metabolizer (EM) phenotypes among children undergoing ARS after failing PPI therapy would differ compared to controls (children with no history of ARS). We conducted a case-control study between children across the Nemours Health System from 2000 to 2014 who received ARS after failing PPI therapy and a control group comprised of healthy children. Our results demonstrated 2.9% of ARSs vs 20.8% of controls were poor metabolizers (PMs), 55.9% of ARSs vs 49.0% of controls were normal metabolizers (NMs), and 41.2% of ARSs vs 30.2% of controls were EMs; p = 0.035. Next, we performed a multiple-regression model to account for race as a potential confounding variable and the EM group was significantly associated with ARS compared to controls (OR 9.78, CI 1.25-76.55, p < 0.03).
conclusionAmong children with medically refractory GERD despite PPI therapy, carriage of CYP2C19*17 allele corresponding to the EM phenotype was associated with ARS. Prospective comparative personalized medicine effectiveness studies are needed to determine if CYP2C19 genotype-guided dosing improves response to PPI therapy without a corresponding increase in adverse effects in children. What is known: • Anti-reflux surgery (ARS) is one of the most common surgical procedures performed in children for the indication of refractory gastroesophageal reflux disease (GERD). What is new: • Individualizing PPI medication dosing based on CYP2C19 diplotype may avoid GERD treatment failures and reduce the need for anti-reflux surgery (ARS).
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