Effects of CYP2C19 loss-of-function variants on the eradication of H. pylori infection in patients treated with proton pump inhibitor-based triple therapy regimens: a meta-analysis of randomized clinical trials

PLoS One. 2013 Apr 30;8(4):e62162. doi: 10.1371/journal.pone.0062162. Print 2013.

Abstract

Background: There are inconsistent conclusions about whether CYP2C19 variants could affect H. pylori eradication rate in patients treated with the proton pump inhibitor (PPI)-based therapy. We therefore performed a meta-analysis of randomized clinical trials (RCTs) to re-evaluate the impact of CYP2C19 variants on PPI-based triple therapy for the above indication.

Methods: All relevant RCTs in the PubMed, Cochrane Library, EMBASE, Web of Science and two Chinese databases (up to February 2013) were systematically searched, and a pooled analysis was performed with the odds ratio (OR) and 95% confidence interval (CI) by the STATA software.

Results: Sixteen RCT datasets derived from 3680 patients were included. There was no significant heterogeneity across the data available in this meta-analysis. There were significant differences in that rate between homozygous (HomEMs) and heterozygous (HetEMs) extensive metabolizers (OR 0.724; 95% CI 0.594-0.881), between HomEMs and poor metabolizers (PM) (OR 0.507; 95%CI 0.379-0.679), or between HetEMs and PMs (OR 0.688; 95%CI 0.515-0.920), regardless of the PPI being taken. Furthermore, sub-analysis of individual PPIs was carried out to explore the difference across all the PPIs used. A significantly low rate was seen in HomEMs vs. HetEMs taking either omeprazole (OR 0.329; 95%CI 0.195-0.553) or lansoprazole (OR 0.692; 95%CI 0.485-0.988), and also in HomEMs vs. PMs for omeprazole (OR 0.232; 95%CI 0.105-0.515) or lansoprazole (OR 0.441; 95%CI 0.252-0.771). However, there was no significant difference between HetEMs and PMs taking either one. No significant differences were observed for rabeprazole or esomeprazole across the CYP2C19 genotypes of interest.

Conclusions: Carriage of CYP2C19 loss-of-function variants is associated with increased H. pylori eradication rate in patients taking PPI-based triple therapies when omeprazole or lansoprazole is chosen. However, there is no a class effect after use of rabeprazole or esomeprazole.

Publication types

  • Meta-Analysis

MeSH terms

  • Anti-Bacterial Agents / therapeutic use*
  • Aryl Hydrocarbon Hydroxylases / genetics*
  • Aryl Hydrocarbon Hydroxylases / metabolism
  • Cytochrome P-450 CYP2C19
  • Drug Therapy, Combination
  • Genetic Variation*
  • Genotype
  • Helicobacter Infections / drug therapy*
  • Helicobacter Infections / genetics*
  • Helicobacter Infections / microbiology
  • Helicobacter pylori / drug effects*
  • Humans
  • Odds Ratio
  • Proton Pump Inhibitors / therapeutic use*
  • Randomized Controlled Trials as Topic
  • Treatment Outcome

Substances

  • Anti-Bacterial Agents
  • Proton Pump Inhibitors
  • Aryl Hydrocarbon Hydroxylases
  • CYP2C19 protein, human
  • Cytochrome P-450 CYP2C19

Grant support

The authors have no support or funding to report.