Pharmacogenet Genomics. 2026 Mar 26. doi: 10.1097/FPC.0000000000000599. Online ahead of print.
ABSTRACT
OBJECTIVES: Gastroesophageal reflux disease is primarily treated with proton pump inhibitors (PPIs), which are metabolized by cytochrome P450 2C19 (CYP2C19) in the liver. CYP2C19 polymorphisms affect PPI plasma levels, with rapid (2-27%) and ultra-rapid (<1-5%) metabolizers needing higher doses, while poor (3-15%) and intermediate (27-47%) metabolizers require lower doses for therapeutic effectiveness. Antireflux surgery is recommended for patients refractory to medical therapy or with symptomatic hiatal hernias.
METHODS: This is a multisite retrospective review of adult patients from 2012 to 2023 diagnosed with gastroesophageal reflux disease who underwent hiatal hernia operations and completed CYP2C19 testing. CYP2C19 phenotypes were grouped as poor metabolizer/intermediate metabolizer, normal metabolizers, or rapid metabolizer/ultra-rapid metabolizer. Hiatal hernia size was classified as small, medium, or large based on preoperative and intra-operative findings. Descriptive statistics were used.
RESULTS: Eighty patients [female: 66%, median age: 60.5 (interquartile range 53.3-67.0) years, 90% White, 6% Hispanic] had CYP2C19 testing and underwent a hiatal hernia repair. CYP2C19 phenotypes were poor metabolizer (4%), intermediate metabolizer (24%), normal metabolizers (30%), rapid metabolizer (31%), and ultra-rapid metabolizer (11%). About 28% were grouped as poor metabolizer/intermediate metabolizer and 43% as rapid metabolizer/ultra-rapid metabolizer. Among patients with small (n = 41) and medium (n = 23) hernias, 39% and 57%, respectively, were classified as rapid metabolizer/ultra-rapid metabolizer, suggesting they were resistant to PPIs.
CONCLUSION: The prevalence of rapid metabolizer/ultra-rapid metabolizer CYP2C19 phenotypes in patients undergoing antireflux surgery is higher than generally reported in the general population. These patients could potentially benefit from higher PPI doses or surgical intervention if ineffective. Prospective multisite studies with diverse, representative samples are needed to confirm these findings.
PMID:42218813 | DOI:10.1097/FPC.0000000000000599
