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Interaction Between IL1B Gene Promoter Polymorphisms in Determining Susceptibility to Helicobacter pylori Associated Duodenal Ulcer

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Title Interaction Between IL1B Gene Promoter Polymorphisms in Determining Susceptibility to Helicobacter pylori Associated Duodenal Ulcer
 
Creator Chakravorty, Meenakshi
Ghosh, Arunima
Choudhury, Abhijit
Santra, Amal
Hembrum, Jobaranjan
Roychoudhury, Susanta
 
Subject Molecular & Human Genetics
 
Description 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 �511TT (NT_022135.14:g.2302610C4T), OR54.22 (95% CI51.8�9.4) and �31CC
(NT_022135.14:g.2302130C4T), OR52.16 (95% CI 1.12�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 (OR52.47, CI51.27�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 (Po0.001) and TT (Po0.001) 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. pyloriinfected
individuals with the �31CC genotype secrete less IL1B and are susceptible to duodenal ulcers. They
also suggest that the allelic interaction between the �511 and �31 polymorphic sites determines the overall
strength of the IL1B promoter.
 
Date 2006
 
Type Article
PeerReviewed
 
Format application/pdf
 
Identifier http://www.eprints.iicb.res.in/412/1/ANTIMICROBIAL_AGENTS_AND_CHEMOTHERAPY%2C_50_(_5)%2C_1788%2D1797_[88].pdf
Chakravorty, Meenakshi and Ghosh, Arunima and Choudhury, Abhijit and Santra, Amal and Hembrum, Jobaranjan and Roychoudhury, Susanta (2006) Interaction Between IL1B Gene Promoter Polymorphisms in Determining Susceptibility to Helicobacter pylori Associated Duodenal Ulcer. Human Mutation, 50 (5). pp. 1788-1797.
 
Relation htpp://dx.doi.org/10.1002/humu.20299
http://www.eprints.iicb.res.in/412/