1. ¹First Department of Medicine, Center for Clinical Research, and Department of Laboratory Medicine, Hamamatsu University School of Medicine, Hamamatsu, Japan
2. ² Department of Clinical Pharmacology and Pharmacy, School of Pharmaceutical Sciences, Teikyo Heisei University, Chiba

Correspondence: Mitsushige Sugimoto, MD, PhD, First Department of Medicine, Hamamatsu University School of Medicine, 1-20-1 Handayama, Hamamatsu, 431-3192, Japan. E-mail: mitsu@hama-med.ac.jp

^*This study was supported by a scientific research grant from the YOKOYAMA Foundation for Clinical Pharmacology; a grant in aid from the Center of Excellence from the Ministry of Education, Culture, Sports, Science and Technology; a grant in aid from the Ministry of Education, Culture, Sports, Science and Technology of Japan (17590470); and a scientific research grant from the Japanese Society for Clinical Pharmacology and Therapeutics.

Received 13 January 2006; Accepted 15 March 2006.

Abstract

Backgrounds and Aims: Polymorphisms of proinflammatory cytokines, such as interleukin (IL) 1 and tumor necrosis factor (TNF) , are associated with individual differences in gastric mucosal inflammation and acid inhibition in response to Helicobacter pylori infection. We investigated whether inflammation-related cytokine polymorphisms would influence the eradication rates of H pylori by a triple-therapy regimen.

Methods: Three hundred sixty patients infected with clarithromycin-sensitive strains of H pylori were genotyped for IL1B -511, IL1RN, TNFA -857/-863/-1031, IL10 -1082/-819/-592, and CYP2C19 and underwent triple therapy for 1 week with a proton pump inhibitor (20 mg omeprazole, 30 mg lansoprazole, or 10 mg rabeprazole) twice daily, 400 mg clarithromycin twice daily, and 750 mg amoxicillin (INN, amoxicilline) twice daily. The influences of the previously mentioned polymorphisms on the eradication rates were analyzed.

Results: The intention-to-treat–based total eradication rate was 83.6% (301/360). The logistic regression analysis revealed that polymorphisms of CYP2C19 and IL1B -511 were independently associated with the eradication rates, but other cytokine polymorphisms were not associated with these rates. The eradication rates in patients with IL1B -511 C/C, C/T, and T/T genotypes were 72.2% (70/97), 87.7% (164/187), and 88.2% (67/76), respectively (P = .0017). When patients were stratified by CYP2C19 genotype status, IL1B -511 genotype–dependent differences in eradication rates were observed in homozygous extensive metabolizers (EMs) but not in heterozygous EMs and poor metabolizers of CYP2C19. The eradication rate in homozygous EM patients with the IL1B -511 C/C genotype was quite low (51.1% [22/43]).

Conclusions: IL1B -511 polymorphism, but not IL1RN, TNFA, or IL10 polymorphism, is one of the determinants of triple therapy for clarithromycin-sensitive strains of H pylori in CYP2C19 homozygous EMs.