The effect of CYP2C19 polymorphisms on H. pylori eradication rate in dual and triple first-line PPI therapies: a meta-analysis.
OBJECTIVE
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.
Padol
Sara
S
Division of Gastroenterology, McMaster University, Hamilton, Ontario, Canada.
Yuan
Yuhong
Y
Thabane
Marroon
M
Padol
Ireneusz T
IT
Hunt
Richard H
RH
D053799:2-Pyridinylmethylsulfinylbenzimidazoles; D000897:Anti-Ulcer Agents / Q000627:therapeutic use*; D001189:Aryl Hydrocarbon Hydroxylases / Q000235:genetics*; D001562:Benzimidazoles / Q000627:therapeutic use; D065731:Cytochrome P-450 CYP2C19; D016481:Helicobacter Infections / Q000188:drug therapy* / Q000235:genetics; D016480:Helicobacter pylori / Q000187:drug effects*; D006801:Humans; D064747:Lansoprazole; D006899:Mixed Function Oxygenases / Q000235:genetics*; D009853:Omeprazole / Q000031:analogs & derivatives / Q000627:therapeutic use; D054328:Proton Pump Inhibitors; D064750:Rabeprazole
D053799:2-Pyridinylmethylsulfinylbenzimidazoles; D000897:Anti-Ulcer Agents; D001562:Benzimidazoles; D054328:Proton Pump Inhibitors; D064747:Lansoprazole; D064750:Rabeprazole; D006899:Mixed Function Oxygenases; D001189:Aryl Hydrocarbon Hydroxylases; C045793:CYP2C19 protein, human; D065731:Cytochrome P-450 CYP2C19; D009853:Omeprazole