Interaction between IL1B gene promoter polymorphisms in determining susceptibility to Helicobacter pylori associated duodenal ulcer

It has been speculated that IL-1 genes play a crucial role in the genetic predisposition to duodenal ulcer upon H. pylori infection by modulating the host immune response. In the present study, 3 10 individuals from Eastern India were subjected to a case-control study to determine the IL1B and IL1RN risk genotypes to H. pylori mediated duodenal ulcer. An analysis of genotype frequency revealed a significantly higher frequency of IL1B -511TT (NIT_022135.14:g.2302610C > T), OR=4.22 (95% CI=1.8-9.4) and -31CC (NT_022135.14:g.2302130C > T), OR = 2.16 (95% CI1.12-4.15) genotypes in H. pylori-infected individuals with duodenal ulcer compared to infected individuals with normal mucosa. Moreover, the T/C haplotype of IL1B-511 and IL1B-31 loci was present in a significantly higher frequency in H. pylori-infected duodenal ulcer patients than in infected controls (OR = 2.47, CI = 1.27-4.8). Quantitative analysis of the mucosal IL1B mRNA revealed that among H. pylori,infected individuals, carriers of the -31CC genotype had significantly lower IL1B transcript levels than carriers of the CT (P < 0.001) and TT (P < 0.001) genotypes, independently of disease status. An IL1B promoter activity assay showed that the promoter with -31T had a 10-fold increase in activity compared to the one with -31C. The IL1B promoter bearing the different combinations of both polymorphic loci showed an interaction between the -511 and -31 loci. Our results show that H. pylori-infected individuals with the -31CC genotype secrete less IL1B and are susceptible to duodenal ulcers. The), also suggest that the allelic interaction between the -511 and -31 polymorphic sites determines the overall strength of the IL1B promoter.