Effect of CYP2C19*17 gene variant on Helicobacter pylori eradication in peptic ulcer patients.
OBJECTIVE
Eradication of Helicobacter pylori is an important treatment strategy in peptic ulcer patients. Current regimens of eradication consist of proton pump inhibitor (PPI) and two antibiotics. The principal enzyme involved in PPIs metabolism is CYP2C19, which exhibits an interindividual variability of activity, mainly due to genetic polymorphism. Two alleles (CYP2C19*2 and CYP2C19*3), responsible for slow PPIs metabolism, were previously associated with higher efficacy of eradication. Recently, a novel CYP2C19 gene variant (CYP2C19*17), associated with faster metabolism of CYP2C19 substrates, was described. In the present study, a potential association between CYP2C19*17 allele and lower H. pylori eradication efficacy was tested in a group of peptic ulcer patients.


METHODS
A total of 125 peptic ulcer patients, positive for H. pylori infection, were treated with triple therapy (pantoprazole+amoxicillin+metronidazole). Subsequently, the patients were divided into two groups (group 1 - success, and group 2 - failure of eradication after therapy) and genotyped for the presence of CYP2C19 variant alleles (*2, *3, and *17).


RESULTS
Frequency of CYP2C19 alleles in two groups of patients were: 56.4 versus 65 (p=0.060) for *1, 15.4 versus 5.3 (p=0.015) for *2, and 28.2 versus 25.5 (p=0.663) for *17 allele, respectively. CYP2C19*3 was not detected in the evaluated population. No significant differences in frequency nor distribution of *17 allele were found between two groups of patients. CYP2C19*2 allele was associated with successful H. pylori eradication (p<0.02), *2 allele carriers were found to be over 4-times more prone to the treatment compared to *1/*1 homozygotes (OR=4.2, p=0.015).


CONCLUSIONS
Our results suggest that, contrary to CYP2C19*2, CYP2C19*17 allele has no impact on efficacy of H. pylori eradication in peptic ulcer patients treated with pantoprazole.
Kurzawski
Mateusz
M
Department of Pharmacology, Pomeranian Medical University, Powstancow Wlkp. 72, 70-111, Szczecin, Poland.
Gawrońska-Szklarz
Barbara
B
Wrześniewska
Joanna
J
Siuda
Andrzej
A
Starzyńska
Teresa
T
Droździk
Marek
M
D053799:2-Pyridinylmethylsulfinylbenzimidazoles / Q000627:therapeutic use; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000483:Alleles; D000658:Amoxicillin / Q000627:therapeutic use; D000900:Anti-Bacterial Agents / Q000627:therapeutic use; D000897:Anti-Ulcer Agents / Q000627:therapeutic use*; D001189:Aryl Hydrocarbon Hydroxylases / Q000235:genetics*; D065731:Cytochrome P-450 CYP2C19; D004359:Drug Therapy, Combination; D005260:Female; D005787:Gene Frequency; D005838:Genotype; D006239:Haplotypes; D016480:Helicobacter pylori / Q000187:drug effects*; D006801:Humans; D008297:Male; D008795:Metronidazole / Q000627:therapeutic use; D008875:Middle Aged; D006899:Mixed Function Oxygenases / Q000235:genetics*; D016017:Odds Ratio; D000077402:Pantoprazole; D010437:Peptic Ulcer / Q000188:drug therapy* / Q000235:genetics / Q000382:microbiology; D011110:Polymorphism, Genetic; D016896:Treatment Outcome
D053799:2-Pyridinylmethylsulfinylbenzimidazoles; D000900:Anti-Bacterial Agents; D000897:Anti-Ulcer Agents; D008795:Metronidazole; D000658:Amoxicillin; D000077402:Pantoprazole; D006899:Mixed Function Oxygenases; D001189:Aryl Hydrocarbon Hydroxylases; C045793:CYP2C19 protein, human; D065731:Cytochrome P-450 CYP2C19