L J Egan1, G M Myhre, D C Mays, R A Dierkhising, P P Kammer, J A Murray. 1. Clinical Pharmacology Unit, Division of Gastroenterology and Hepatology and Division of Biostatistics, Mayo Clinic, Rochester, Minnesota 55905, USA. egan.laurence@mayo.edu
Abstract
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.
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:GERDpatients 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 GERDpatients. 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.
Authors: Nicole G Hunfeld; Ron A Mathot; Daan J Touw; Ron H van Schaik; Paul G Mulder; Paul F Franck; Ernst J Kuipers; William P Geus Journal: Br J Clin Pharmacol Date: 2008-01-30 Impact factor: 4.335
Authors: Diana M Orbelo; Felicity T Enders; Yvonne Romero; Dawn L Francis; Sami R Achem; Tushar S Dabade; Michael D Crowell; Debra M Geno; Ramona S DeJesus; Vikneswaran Namasivayam; Steven C Adamson; Amindra S Arora; Andrew J Majka; Jeffrey A Alexander; Joseph A Murray; Matthew Lohse; Nancy N Diehl; Mary Fredericksen; Kee Wook Jung; Margaret S Houston; Angela E O'Neil; David A Katzka Journal: Dig Dis Sci Date: 2014-01-22 Impact factor: 3.199