title: Interleukin-1beta genetic polymorphism influences the effect of cytochrome P 2C19 genotype on the cure rate of 1-week triple therapy for Helicobacter pylori infection.
abstract: OBJECTIVE
  Genetic polymorphism of interleukin (IL)-1beta is associated with differences in gastric acid suppression in response to Helicobacter pylori (H. pylori) infection. Thus, the polymorphism might affect H. pylori eradication therapy, as antibiotics used in treatment regimens may be acid sensitive. In this study, we examined the impact of IL-1beta genetic polymorphism on the cure rate of triple therapy for H. pylori in relation to cytochrome P (CYP) 2C19 genotype and antibiotic resistance.
  
  
  METHODS
  A total 249 patients with peptic ulcer disease were randomized to receive one of the following regimens: amoxicillin and clarithromycin together with omeprazole, lansoprazole, or rabeprazole. CYP2C19 and IL-1beta-511 genetic polymorphisms were analyzed by polymerase chain reaction-restriction fragment length polymorphism.
  
  
  RESULTS
  The intention-to-treat-based overall cure rate was 74.3% (95% CI=68-79%). In the normal acid secretion IL-1beta genotype group, the cure rate among CYP2C19 poor metabolizers (93.3%, 95% CI=56-99%) was significantly higher than among subjects in the CYP2C19 homozygous (60.0%, 95% CI=38-78%) and heterozygous (63.6%, 95% CI=46-78%), i.e., extensive metabolizer, groups (p<0.05). In the low acid secretion IL-1beta genotype group, there was no difference in the cure rate among the CYP2C19 genotype groups. Multiple logistic regression analysis identified susceptibility to clarithromycin (p<0.0001) and CYP2C19 genotype status (p=0.03) as significant independent factors for treatment failure.
  
  
  CONCLUSIONS
  IL-1beta genetic polymorphism, although not an independent factor in treatment outcome, influences the impact of the CYP2C19 genotype on the cure rate of 1-wk triple therapy for H. pylori infection.
authors.affiliation: Department of Medicine and Medical Science, Okayama University Graduate School of Medicine and Dentistry, Okayama, Japan.
authors.forename: Susumu
authors.initials: S
authors.lastname: Take
authors.forename: Motowo
authors.initials: M
authors.lastname: Mizuno
authors.forename: Kuniharu
authors.initials: K
authors.lastname: Ishiki
authors.forename: Yasuhiro
authors.initials: Y
authors.lastname: Nagahara
authors.forename: Tomowo
authors.initials: T
authors.lastname: Yoshida
authors.forename: Tomoki
authors.initials: T
authors.lastname: Inaba
authors.forename: Kazuhide
authors.initials: K
authors.lastname: Yamamoto
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Okada
authors.forename: Kenji
authors.initials: K
authors.lastname: Yokota
authors.forename: Keiji
authors.initials: K
authors.lastname: Oguma
authors.forename: Yasushi
authors.initials: Y
authors.lastname: Shiratori
mesh_terms: D053799:2-Pyridinylmethylsulfinylbenzimidazoles; D000293:Adolescent; D000328:Adult; D000658:Amoxicillin / Q000627:therapeutic use; D001189:Aryl Hydrocarbon Hydroxylases / Q000235:genetics*; D001562:Benzimidazoles / Q000627:therapeutic use; D017291:Clarithromycin / Q000627:therapeutic use; D065731:Cytochrome P-450 CYP2C19; D004359:Drug Therapy, Combination / Q000627:therapeutic use*; D005260:Female; D005500:Follow-Up Studies; D005838:Genotype; D016481:Helicobacter Infections / Q000188:drug therapy* / Q000235:genetics; D016480:Helicobacter pylori / Q000187:drug effects / Q000302:isolation & purification; D006801:Humans; D007375:Interleukin-1 / Q000235:genetics*; D064747:Lansoprazole; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D006899:Mixed Function Oxygenases / Q000235:genetics*; D015999:Multivariate Analysis; D009853:Omeprazole / Q000031:analogs & derivatives* / Q000627:therapeutic use; D011110:Polymorphism, Genetic; D011336:Probability; D054328:Proton Pump Inhibitors; D017494:Proton Pumps / Q000627:therapeutic use; D064750:Rabeprazole; D018709:Statistics, Nonparametric; D016896:Treatment Outcome
chemical_list: D053799:2-Pyridinylmethylsulfinylbenzimidazoles; D001562:Benzimidazoles; D007375:Interleukin-1; D054328:Proton Pump Inhibitors; D017494:Proton Pumps; D064747:Lansoprazole; D064750:Rabeprazole; D000658:Amoxicillin; D006899:Mixed Function Oxygenases; D001189:Aryl Hydrocarbon Hydroxylases; C045793:CYP2C19 protein, human; D065731:Cytochrome P-450 CYP2C19; D017291:Clarithromycin; D009853:Omeprazole