Influence of IL-1 gene cluster polymorphisms on the development of H. pylori associated gastric ulcer.
OBJECTIVE
Chronic H. pylori infection is the main cause of ulcer disease which depicts a major burden of our healthy care systems. The individual host immune response plays a pivotal role in the outcome of the infection but genetic susceptibility to develop gastric ulcer is unknown. IL-1beta and its natural receptor antagonist IL-1ra are involved in the inflammatory response to H. pylori infection. Thus, we investigated the influence of functional genetic variants in the IL-1 gene cluster on the development of gastric ulcer disease.


METHODS
390 H. pylori infected patients were genotyped for IL-1B -31 and +3954 by TaqMan technology. Alleles of IL-1RN 86VNTR were determined by gel electrophoresis after amplification. Three hundred and sixty healthy blood donors were included as healthy controls.


RESULTS
Carriage of the IL-1B -31 C allele conferred a increased but not significant risk for H. pylori infection (OR: 1.3, Wald 95% CI: 0.8<OR<2.1). Patients carrying short allele 2 of IL-1RN had a 1.6-fold significantly increased risk for the development of gastric ulcer (Pearson's=4.0, p=0.044, OR: 1.6, Wald 95% CI: 1.0<OR<2.4).


CONCLUSIONS
Our results underline the crucial role of the host immune response to H. pylori infection and confirm the importance of polymorphisms in the IL-1 cluster as a factor to give rise to different clinical outcomes. Further studies are needed to fully understand the pathophysiological effect of polymorphisms in the IL-1 cluster in H. pylori associated ulcer disease and susceptibility to infection itself.
Hellmig
Stephan
S
Department of General Internal Medicine, University Clinics of Schleswig-Holstein, Campus Kiel, Schittenhelmstrasse 12, 24105 Kiel, Germany. s.hellmig@mucosa.de
Titz
Andrea
A
Steinel
Stefanie
S
Ott
Stephan
S
Fölsch
Ulrich Robert
UR
Hampe
Jochen
J
Schreiber
Stefan
S
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D005838:Genotype; D016481:Helicobacter Infections / Q000235:genetics / Q000276:immunology*; D016480:Helicobacter pylori; D006801:Humans; D007375:Interleukin-1 / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D005810:Multigene Family; D011110:Polymorphism, Genetic; D013276:Stomach Ulcer / Q000235:genetics / Q000276:immunology*
D007375:Interleukin-1