The Effect of CYP2C19 Polymorphisms on H. Pylori Eradication Rate in Dual and Triple First-Line PPI Therapies: A Meta-Analysis

Am J Gastroenterol. 2006 Jul;101(7):1467-75. doi: 10.1111/j.1572-0241.2006.00717.x.

Abstract

Premise: It has been suggested that proton pump inhibitor (PPI)-related differences in Helicobacter pylori eradication rates are partly because of CYP2C19 polymorphisms and there have been conflicting data in this area. We conducted a meta-analysis to investigate the evidence relating CYP2C19 to first-line H. pylori eradication rates.

Methods: A search of the literature was conducted up to June 2005 using Medline, EMBase, and Cochrane Register of Controlled Trials (CENTRAL). Twenty-eight arms from 17 papers were extracted for omeprazole, lansoprazole, and rabeprazole, collectively. Review Manager 4.2.8 was used for analysis.

Results: When all eradication rates, regardless of PPI used, were combined there was no significant difference between poor metabolizers (PM) and heterozygous extensive metabolizers (HetEMs) (odds ratio [OR]= 1.35, 95% confidence interval [CI] 0.89-2.07, p = 0.15); however, there was a significant difference between HetEM and homozygous extensive metabolizers (HomEMs) (OR = 1.90, 95% CI 1.38-2.60, p < 0.0001). Significant heterogeneity was observed in a HomEM and PM comparison, hence additional subanalysis of individual PPIs revealed that dual and triple omeprazole therapies significantly favored higher H. pylori eradication rates in PM over HomEM (OR = 4.03, 95% CI 1.97-8.28, p = 0.0001), and also over HetEM (OR = 2.24, 95% CI 1.09-4.61, p = 0.03). Dual and triple rabeprazole and triple lansoprazole therapies did not show significantly different H. pylori eradication rates between PM and HomEM (OR = 1.04, 95% CI 0.44-2.46, p = 0.25) and (OR = 1.80, 95% CI 0.67-4.85, p = 0.93), respectively.

Conclusions: The impact of CYP2C19 polymorphisms on H. pylori eradication rates in studied populations appears clinically relevant in patients prescribed omeprazole as a component of their dual- or triple-drug therapy, whereas regimens that include lansoprazole or rabeprazole are unaffected. The choice of PPI and/or dose rather than CYP2C19 genotyping could be a more practical approach to assure the highest H. pylori eradication rates in clinical settings.

Publication types

  • Meta-Analysis

MeSH terms

  • 2-Pyridinylmethylsulfinylbenzimidazoles
  • Anti-Ulcer Agents / therapeutic use*
  • Aryl Hydrocarbon Hydroxylases / genetics*
  • Benzimidazoles / therapeutic use
  • Cytochrome P-450 CYP2C19
  • Helicobacter Infections / drug therapy*
  • Helicobacter Infections / genetics
  • Helicobacter pylori / drug effects*
  • Humans
  • Lansoprazole
  • Mixed Function Oxygenases / genetics*
  • Omeprazole / analogs & derivatives
  • Omeprazole / therapeutic use
  • Proton Pump Inhibitors
  • Rabeprazole

Substances

  • 2-Pyridinylmethylsulfinylbenzimidazoles
  • Anti-Ulcer Agents
  • Benzimidazoles
  • Proton Pump Inhibitors
  • Lansoprazole
  • Rabeprazole
  • Mixed Function Oxygenases
  • Aryl Hydrocarbon Hydroxylases
  • CYP2C19 protein, human
  • Cytochrome P-450 CYP2C19
  • Omeprazole