Interaction between IL1B gene promoter polymorphisms in determining susceptibility to Helicobacter pylori associated duodenal ulcer
✍ Scribed by Meenakshi Chakravorty; Arunima Ghosh; Abhijit Choudhury; Amal Santra; Jobaranjan Hembrum; Susanta Roychoudhury
- Publisher
- John Wiley and Sons
- Year
- 2006
- Tongue
- English
- Weight
- 300 KB
- Volume
- 27
- Category
- Article
- ISSN
- 1059-7794
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✦ Synopsis
Communicated by Stephen Chanock
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, 310 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 À511TT (NT_022135.14:g.2302610C4T), OR 5 4.22 (95% CI 5 1.8À9.4) and À31CC (NT_022135.14:g.2302130C4T), OR 5 2.16 (95% CI 1.12À4.15) genotypes in H. pylori-infected individuals with duodenal ulcer compared to infected individuals with normal mucosa. Moreover, the T/C haplotype of IL1B À511 and IL1B À31 loci was present in a significantly higher frequency in H. pylori-infected duodenal ulcer patients than in infected controls (OR 5 2.47, CI 5 1.27À4.8). Quantitative analysis of the mucosal IL1B mRNA revealed that among H. pylori-infected individuals, carriers of the À31CC genotype had significantly lower IL1B transcript levels than carriers of the CT (Po0.001) and TT (Po0.001) genotypes, independently of disease status. An IL1B promoter activity assay showed that the promoter with À31T had a 10-fold increase in activity compared to the one with À31C. The IL1B promoter bearing the different combinations of both polymorphic loci showed an interaction between the À511 and À31 loci. Our results show that H. pyloriinfected individuals with the À31CC genotype secrete less IL1B and are susceptible to duodenal ulcers. They also suggest that the allelic interaction between the À511 and À31 polymorphic sites determines the overall strength of the IL1B promoter. Hum Mutat 27(5), 411-419, 2006. r