Influence of cytochrome P450 2C19 genetic polymorphism and dosage of rabeprazole on accuracy of proton-pump inhibitor testing in Chinese patients with gastroesophageal reflux disease

Abstract

Background and Aim: To evaluate the optimal dosage of rabeprazole for proton-pump inhibitor (PPI) testing of gastroesophageal reflux disease (GERD) and to test the influence of cytochrome P450 (CYP) 2C19 polymorphism in a population with a high prevalence of people who metabolize PPI poorly. Methods: In this randomized, open-label trial, patients with symptoms suggestive of GERD were randomized to receive a 2-week test with 20- or 40-mg rabeprazole after diagnostic endoscopy. Symptom response was assessed with a four-grade daily record; in addition, DNA from peripheral blood leukocytes was genotyped for CYP2C19 polymorphism with the polymerase chain reaction-restriction fragment length polymorphism technique. Results: Of the 164 patients who completed the study, 69 (42.1%) were endoscopically positive for esophagitis; the remaining 95 (57.9%) were diagnosed with endoscopy-negative reflux disease. Based on the best cut-off value for 50% symptom reduction, the sensitivity, specificity, positive predictive value, negative predictive value, and accuracy for detecting erosive esophagitis were 68%, 70%, 66%, 72%, and 69%, respectively, for the 20-mg regimen, and 84%, 71%, 64%, 88%, and 76%, respectively, for the 40-mg regimen, a non-significant difference. Regarding the genotype, 60 (39%) patients had two wild-type alleles, 63 (40.9%) had one variant allele, and 31 (20.1%) had two variant CYP2C19 alleles. The presence of a variant allele did not alter the diagnostic efficacy of PPI testing. Conclusions: Both dose levels of rabeprazole proved efficacious in the diagnosis of GERD. Various measures of test accuracy were unrelated to the status of the CYP2C19 genotype. © 2007 The Authors.