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

Abstract

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 a (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-1B2511T 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 2511C 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.

The role of interleukin-1 gene polymorphisms and Helicobacter pylori in gastroesophageal reflux disease

“…Some recent researches revealed the association between specific proinflammatory polymorphisms in genes and GERD. IL-1β (-31) polymorphic allele and IL-1RN2 are demontrated to be negatively correlated to GERD (9). In a well organized study it has been shown that there is not any difference of IL-1β (-511) polymorphism among patients with Barrett's esophagus, GERD or gastric adenocarcinoma (10).…”

“…In a well organized study it has been shown that there is not any difference of IL-1β (-511) polymorphism among patients with Barrett's esophagus, GERD or gastric adenocarcinoma (10). Among healthy persons, important inter-individual variations were seen in pro-inflammatory proteins especially in in-vitro production (9). Numerous reseraches have shown the impact of polymorphisms of IL-1β and IL-1RN on the development of GERD (16).…”

“…A recent study from Taiwan concluded that, IL-1β (-511) T/T (-31) C/C genotypes, IL-1β (-511) T and (-31) C alleles had been almost all related to an increased likelihood of the presence of reflux esophagitis (18). In addition, it has been often demonstrated that the existence of HP infection together with proinflammatory IL-1ß (-511) T/T allele is correlated to decreased likelihood of GERD by inducing atrophy in the gastric corpus (9,10).…”

Interleukin-1β and Interleukin-1 Receptor Antagonist Gene Polymorphisms and Gastric Cancer: A Meta-analysis

“…Inverse associations between IL1BÀ511T/À31C and gastroesophageal reflux disease risk have been recently reported (73,74). It is reasonable that alleles associated with gastric cancer and gastric atrophy would also be associated with a decrease in risk of an acid-related condition, such as gastroesophageal reflux disease.…”

Does Helicobacter pylori protect against oesophageal adenocarcinoma, and if so, how?

“…18 Several studies have shown that these polymorphisms, as would be expected, offer relative protection against reflux oesophagitis and its complications in H. pyloriinfected people. [19][20][21] In developed countries, individuals are infected with H. pylori strains of differing pathogenicity. The most pathogenic strains increase the risk of peptic ulceration and gastric adenocarcinoma largely through increasing gastric inflammation, and as the corpus is often involved these strains most commonly suppress acid production.…”