CYP2C19 pharmacogenetics in the clinical use of proton-pump inhibitors for gastro-oesophageal reflux disease: Variant alleles predict gastric acid suppression, but not oesophageal acid exposure or reflux symptoms

Background: The rate of metabolic inactivation of proton-pump inhibitors is determined by polymorphisms of CYP2C19. It is not known if CYP2C19 variant alleles affect responses to proton-pump inhibitor therapy in gastro-oesophageal reflux disease (GERD). Aim: To determine if the CYP2C19 genotype is associated with clinical effectiveness of proton-pump inhibitors during GERD therapy. Methods: GERD patients undergoing ambulatory gastric and oesophageal pH monitoring were genotyped for CYP2C19 polymorphisms. Results: Sixty subjects were enrolled. Forty-four subjects had two wild-type alleles, 15 had one variant, and one had two variant CYP2C19 alleles. The presence of a variant allele was significantly associated with a lower odds of gastric acid breakthrough during proton-pump inhibitor therapy [odds ratio 5.14, 95% confidence interval (CI) 1.17-22.61]. The presence of a variant allele was not associated with a lower odds of significant oesophageal acid exposure (odds ratio 2.50, 95% CI 0.60-10.52), or the occurrence of symptoms (incidence rate ratio 1.06, 95% CI 0.54-2.06). Conclusions: These results indicate that factors other than gastric acid secretion are important determinants of reflux in GERD patients. This suggests that CYP2C19 genotype testing will not be useful in proton-pump inhibitor therapy of GERD, except perhaps in identifying patients at risk for hypochlorhydria and consequent hypergastrinemia.