Interleukin 1B proinflammatory genotypes protect against gastro-oesophageal reflux disease through induction of corpus atrophy.
OBJECTIVE
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 alpha (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.
Ando
T
T
Department of Gastroenterology, Nagoya University Graduate School of Medicine, Nagoya, Japan. takafumia-gi@umin.ac.jp
El-Omar
E M
EM
Goto
Y
Y
Nobata
K
K
Watanabe
O
O
Maeda
O
O
Ishiguro
K
K
Minami
M
M
Hamajima
N
N
Goto
H
H
D000328:Adult; D004941:Esophagitis / Q000235:genetics / Q000382:microbiology; D005260:Female; D005757:Gastritis, Atrophic / Q000150:complications / Q000235:genetics* / Q000382:microbiology; D005764:Gastroesophageal Reflux / Q000235:genetics* / Q000382:microbiology / Q000517:prevention & control; D020022:Genetic Predisposition to Disease; D005838:Genotype; D016481:Helicobacter Infections / Q000150:complications; D016480:Helicobacter pylori; D006801:Humans; D007375:Interleukin-1 / Q000235:genetics*; D016753:Interleukin-10 / Q000235:genetics; D008297:Male; D008875:Middle Aged; D016133:Polymerase Chain Reaction / Q000379:methods; D011446:Prospective Studies; D012720:Severity of Illness Index; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics
D007375:Interleukin-1; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10