Interleukin-1β Genetic Polymorphism Influences the Effect of Cytochrome P 2C19 Genotype on the Cure Rate of 1-Week Triple Therapy for Helicobacter pylori Infection

Susumu Take, Motowo Mizuno, Kuniharu Ishiki, Yasuhiro Nagahara, Tomowo Yoshida, Tomoki Inaba, Kazuhide Yamamoto, Hiroyuki Okada, Kenji Yokota, Keiji Oguma, Yasushi Shiratori

Research output: Contribution to journalArticle

63 Citations (Scopus)

Abstract

OBJECTIVES: Genetic polymorphism of interleukin (IL)-1β 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-1β 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-1β-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-1β 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-1β 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. CONCLUSION: IL-1β 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.

Original languageEnglish
Pages (from-to)2403-2408
Number of pages6
JournalAmerican Journal of Gastroenterology
Volume98
Issue number11
DOIs
Publication statusPublished - Nov 2003
Externally publishedYes

ASJC Scopus subject areas

  • Hepatology
  • Gastroenterology

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