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.
OBJECTIVE
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.
Lee
Yi-Chia
YC
Department of Internal Medicine, College of Medicine, National Taiwan University, Taipei, Taiwan.
Lin
Jaw-Town
JT
Wang
Hsiu-Po
HP
Chiu
Han-Mo
HM
Wu
Ming-Shiang
MS
D053799:2-Pyridinylmethylsulfinylbenzimidazoles / Q000627:therapeutic use*; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000897:Anti-Ulcer Agents / Q000627:therapeutic use*; D001189:Aryl Hydrocarbon Hydroxylases / Q000235:genetics*; D065731:Cytochrome P-450 CYP2C19; D004942:Esophagitis, Peptic / Q000175:diagnosis / Q000188:drug therapy / Q000235:genetics; D004945:Esophagoscopy; D005260:Female; D005764:Gastroesophageal Reflux / Q000175:diagnosis* / Q000188:drug therapy / Q000235:genetics*; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D006899:Mixed Function Oxygenases / Q000235:genetics*; D011110:Polymorphism, Genetic; D011237:Predictive Value of Tests; D054328:Proton Pump Inhibitors; D064750:Rabeprazole; D012680:Sensitivity and Specificity
D053799:2-Pyridinylmethylsulfinylbenzimidazoles; D000897:Anti-Ulcer Agents; D054328:Proton Pump Inhibitors; D064750:Rabeprazole; D006899:Mixed Function Oxygenases; D001189:Aryl Hydrocarbon Hydroxylases; C045793:CYP2C19 protein, human; D065731:Cytochrome P-450 CYP2C19