The polymorphic IL-1B and IL-1RN genes in the aetiopathogenesis of peptic ulcer

Besides environmental factors, the genetic background of an individual may contribute to the development and final outcome of peptic ulcer disease. In terleukin-1 beta (IL-1 beta) and the interleukin-1 receptor antagonist (IL- 1ra) are cytokines that play a key role in modulating the inflammatory resp onse in the gastrointestinal mucosa. This study aimed to investigate whethe r polymorphisms in the IL-1B and IL-RN genes are involved in the susceptibi lity to and final outcome of peptic ulcer disease. DNA from 179 unrelated S panish Caucasian patients with peptic ulcer diseases and 99 ethnically matc hed healthy controls was typed for the TaqI polymorphism at position + 3954 in the IL-1B gene and the variable number of tandem repeats polymorphism i n intron 2 of the IL-1RN gene. The determination of Helicobacter pylori sta tus and non-steroidal anti-inflammatory drug (NSAIDs) use was studied in al l patients and in controls. H. pylori infection and NSAID use were more fre quent in ulcer patients than in controls. There were no significant differe nces in carriage rate, genotype and allele frequencies of the IL-1RN and th e IL-1B(+3954) gene polymorphisms between peptic ulcer patients and control s. However, a strong allelic association between IL-1B and IL-1RN genes was found in duodenal ulcer patients (P < 0.0006). Logistic regression identif ied H. pylori infection and NSAIDs use as independent risk factors for pept ic ulcer diseases whereas the simultaneous carriage of IL-1B(+3954) allele 2 and IL-1RN allele 2 was associated with reduced risk for duodenal ulcer d isease (OR: 0.37, 95% CI = 0.14-0.9). Our data suggest that IL-1B and IL-1R N genes in addition to bacterial and environmental factors play a key role in determining the final outcome of peptic ulcer disease.