High Prevalence of CYP2C19 Rapid and Ultrarapid Metabolism Among Patients With Gastroesophageal Reflux Disease

Gastroesophageal reflux disease (GERD) is one of the most diagnosed diseases in the United States. A large proportion of patients have an inadequate response to proton pump inhibitors (PPIs), despite the optimization of dosing and timing. We hypothesized that such an inadequate response is often due to polymorphisms in cytochrome P450 2C19 (CYP2C19, CYP). This study aimed to assess the prevalence of rapid CYP metabolism in patients with GERD.

We conducted a single-center retrospective study on patients in an outpatient gastroenterology clinic with GERD who underwent CYP testing between 2019 and 2024. We collected data on CYP genotype, PPI dosing before and after CYP testing, endoscopy results, pH testing, and documentation of symptomatic improvement. Rapid and ultrarapid metabolizers were grouped as "rapid metabolizers," whereas normal and intermediate metabolizers were grouped as "normal metabolizers."

In total, 421 patients with GERD who underwent CYP testing were included in the study. The prevalence of rapid metabolizers was 44% (n =184). The prevalence of Barrett's esophagus/erosive esophagitis was higher among ultrarapid metabolizers (24%; n = 5/21) than among normal metabolizers (7%; n = 12/165; odds ratio, 3.5; 95% confidence interval, 1.1-11.5; P = .0371). There was a nonstatistically significant trend towards higher odds of erosive esophagitis resolution when PPI was adjusted based on CYP results (odds ratio, 9.3; 95% confidence interval, 1.0-90; P = .081).

A large proportion of patients with GERD who underwent CYP2C19 genotyping were rapid metabolizers of CYP2C19 and responded well to changing/adjusting PPIs accordingly.