IL-1 beta pro-inflammatory genotypes protect against gastro-oesophageal reflux disease through induction of corpus atrophy

TAKAFUMI ANDO ¹, Emad M El-Omar ^2*, Yasuyuki Goto ¹, Kazuo Nobata ¹, Osamu Watanabe ¹, Osamu Maeda ¹, Kazuhiro Ishiguro ¹, Masaaki Minami ¹, Nobuyuki Hamajima ¹ and Hidemi Goto ¹

¹ Nagoya University Graduate School of Medicine, Japan
² UNIVERSITY OF ABERDEEN, United Kingdom

^* To whom correspondence should be addressed. E-mail: e.el-omar{at}abdn.ac.uk.

Accepted 16 August 2005

Abstract

Background & 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 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 by 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 TNF-A genes were genotyped.

Results: Two hundred and eight patients were H. pylori positive and 112 were negative. One hundred 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 to 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 pro-inflammatory alleles IL-1B-511T had significantly lower risk of erosive oesophagitis (OR 0.06, 95% CI: 0.006-0.51, p=0.01) and GORD symptoms (OR 0.10, 95% CI: 0.01-0.85, p=0.04) compared to those homozygous for the -511C alleles, while none of the 2 other pro-inflammatory cytokine gene polymorphisms had significant correlations with erosive oesophagitis or GORD symptoms.

Conclusions: A pro-inflammatory IL-1B genotype is associated with increased risk of atrophy and a 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.

Keywords: gastric atrophy, gastro-oesophageal reflux disease, genetic polymorphisms, Helicobacter pylori, interleukin-1 beta

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