STOMACH

Interleukin 1B proinflammatory genotypes protect against gastro-oesophageal reflux disease through induction of corpus atrophy

T Ando¹, E M El-Omar³, Y Goto², K Nobata¹, O Watanabe¹, O Maeda¹, K Ishiguro¹, M Minami¹, N Hamajima⁴, H Goto¹

¹ Department of Gastroenterology, Nagoya University Graduate School of Medicine, Nagoya, Japan
² Department of Gastroenterology, Nagoya University Graduate School of Medicine, Nagoya, Japan, and Department of Preventive Medicine, Biostatistics, and Medical Decision Making, Nagoya University Graduate School of Medicine, Nagoya, Japan
³ Department of Medicine and Therapeutics, University of Aberdeen, Aberdeen, UK
⁴ Department of Preventive Medicine, Biostatistics and Medical Decision Making, Nagoya University Graduate School of Medicine, Nagoya, Japan

Correspondence to:
Dr T Ando
65 Tsurumai-cho, Showa-ku, Nagoya, 466-8550 Japan; takafumia-gi{at}umin.ac.jp

Background and aims: The relationship between Helicobacter pylori infection and gastro-oesophageal reflux disease (GORD) is controversial but it is accepted that GORD is associated with increased exposure to gastric acidity. The proinflammatory interleukin (IL)-1B polymorphisms increase the risk of hypochlorhydria and gastric atrophy. We examined the association between proinflammatory cytokine gene polymorphisms, presence of gastric atrophy, and risk of GORD in H pylori positive and negative subjects in Japan.

Methods: We studied 320 consecutive dyspeptic patients without peptic ulcers or cancers. GORD symptoms were scored using the Carlsson-Dent questionnaire and erosive oesophagitis was assessed endoscopically. H pylori infection was diagnosed by urea breath test, histological examination, and serology. Gastric atrophy was assessed histologically, and polymorphisms in the IL-1B, IL-10, and tumour necrosis factor (TNF-A) genes were genotyped.

Results: Two hundred and eight patients were H pylori positive and 112 were negative. One hundred and eight (34%) were found to have erosive oesophagitis by endoscopic criteria (grade A: 78; grade B: 23; grade C: 6; grade D: 1). Erosive oesophagitis and GORD symptoms were significantly more common in H pylori negative compared with H pylori positive subjects (p<0.05). H pylori positive subjects were more likely to have corpus gastric atrophy than H pylori negative subjects (p<0.001). Among H pylori positive patients, those without erosive oesophagitis or GORD symptoms were significantly more likely to have corpus atrophy than subjects with erosive oesophagitis or GORD symptoms (p<0.05). Among H pylori positive patients, subjects homozygous for the proinflammatory allele IL-1B–511T had a significantly lower risk of erosive oesophagitis (odds ratio (OR) 0.06 (95% confidence interval (CI) 0.006–0.51); p = 0.01) and GORD symptoms (OR 0.10 (95% CI 0.01–0.85); p = 0.04) compared with those homozygous for the –511C allele, while none of the two other proinflammatory cytokine gene polymorphisms had significant correlations with erosive oesophagitis or GORD symptoms.

Conclusions: A proinflammatory IL-1B genotype is associated with increased risk of atrophy and decreased risk of GORD in H pylori infected subjects in Japan. These data indicate that in some genetically predisposed subjects, H pylori infection may protect against GORD through induction of gastric atrophy.

Abbreviations: GORD, gastro-oesophageal reflux disease; IL, interleukin; NERD, non-erosive reflux disease; TNF-, tumour necrosis factor ; ELISA, enzyme linked immunosorbent assay; PCR, polymerase chain reaction; OR, odds ratio

Keywords: gastro-oesophageal reflux disease; Helicobacter pylori; gastric atrophy; genetic polymorphisms; interleukin 1ß

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