Effects of CYP2C19, MDR1, and interleukin 1-B gene variants on the eradication rate of Helicobacter pylori infection by triple therapy with pantoprazole, amoxicillin, and metronidazole.
OBJECTIVE
Eradication of H. pylori is an important treatment strategy in peptic ulcer patients. Current regimens of eradication consist of proton pump inhibitor (PPI) and two antibiotics. Effects of PPI may depend on their metabolism, and other factors important for the pathophysiology of peptic ulcer disease. Aim of the present study was to evaluate an association of CYP2C19, MDR1, and IL-1B polymorphisms with the eradication rate of H. pylori in Polish Caucasian patients treated with a triple therapy of pantoprazole, amoxicillin, and metronidazole.


METHODS
A total of 139 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 by the PCR-RFLP method for the presence of CYP2C19 variant alleles (*2, *3, and *17), and MDR1 3435C>T and IL-1B +3954C>T polymorphisms. Pantoprazole serum concentrations were measured using the HPLC method.


RESULTS
No significant differences in frequency or distribution of CYP2C19 genotypes were found between the two groups of patients (i.e., with successful H. pylori eradication and treatment failure). However, any carrier of defective CYP2C19*2/*2 genotype was found among patients with treatment failure. Similarly, MDR1 and IL-1B genotypes were found to be significantly associated with the success or failure of H. pylori eradication. Univariate and multivariate analysis of the genotypes did not reveal any significant association between the genotypes and H. pylori eradication. Pantoprazole concentrations differed significantly, and were the highest in patients with defective allele CYP2C19*2 carriers and lowest in hyperactive genotype homozygotes CYP2C19*17/*17.


CONCLUSIONS
The results suggest that the CYP2C19 genotype contrary to MDR1 and IL-1B genotypes may have an impact on the efficacy of H. pylori eradication in peptic ulcer patients treated with pantoprazole in Polish Caucasian peptic ulcer patients administered pantoprazole, amoxicillin, and metronidazole.
Gawrońska-Szklarz
Barbara
B
Department of Pharmacology, Pomeranian Medical University, Powstancow Wlkp. 72, 70-111, Szczecin, Poland.
Siuda
Andrzej
A
Kurzawski
Mateusz
M
Bielicki
Dariusz
D
Marlicz
Wojciech
W
Droździk
Marek
M
D053799:2-Pyridinylmethylsulfinylbenzimidazoles / Q000008:administration & dosage* / Q000097:blood; D018435:ATP Binding Cassette Transporter, Subfamily B; D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000235:genetics*; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000658:Amoxicillin / Q000008:administration & dosage*; D000900:Anti-Bacterial Agents / Q000008:administration & dosage; D001189:Aryl Hydrocarbon Hydroxylases / Q000235:genetics*; D065731:Cytochrome P-450 CYP2C19; D004359:Drug Therapy, Combination; D005260:Female; D014644:Genetic Variation; D005838:Genotype; D016481:Helicobacter Infections / Q000188:drug therapy* / Q000235:genetics* / Q000382:microbiology; D016480:Helicobacter pylori / Q000187:drug effects; D006801:Humans; D053583:Interleukin-1beta / Q000235:genetics*; D008297:Male; D008795:Metronidazole / Q000008:administration & dosage*; D008875:Middle Aged; D000077402:Pantoprazole; D010437:Peptic Ulcer / Q000188:drug therapy* / Q000382:microbiology; D011044:Poland; D054328:Proton Pump Inhibitors / Q000008:administration & dosage / Q000097:blood; D017211:Treatment Failure; D044465:White People / Q000235:genetics
D053799:2-Pyridinylmethylsulfinylbenzimidazoles; C513055:ABCB1 protein, human; D018435:ATP Binding Cassette Transporter, Subfamily B; D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D000900:Anti-Bacterial Agents; C508585:IL1B protein, human; D053583:Interleukin-1beta; D054328:Proton Pump Inhibitors; D008795:Metronidazole; D000658:Amoxicillin; D000077402:Pantoprazole; D001189:Aryl Hydrocarbon Hydroxylases; C045793:CYP2C19 protein, human; D065731:Cytochrome P-450 CYP2C19