Interaction betweenIL1Bgene promoter polymorphisms in determining susceptibility toHelicobacter pyloriassociated duodenal ulcer

Abstract

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.2302610C>T), OR=4.22 (95% CI=1.8-9.4) and -31CC (NT_022135.14:g.2302130C>T), OR=2.16 (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 (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. They also suggest that the allelic interaction between the -511 and -31 polymorphic sites determines the overall strength of the IL1B promoter.

Association of Interleukin-1β and Gene Polymorphisms with Liver Pathogenesis in Hepatitis B Virus Infection among Eastern Indian Population

“…30 Another study from Eastern India showed that IL-1b À511TT and À31CC genotypes were significantly associated with Helicobacter pylori infected individuals with duodenal ulcer, and also stated that T/C haplotype at the IL-1b À511/À31 loci is mostly prevalent in Indian population. 32 Interestingly the frequency of proinflammatory À511TT genotype is widespread in the study population (38.23%, data not shown). The higher occurrence of the said genotype in the study population might be a crucial factor that influence poorer clinical outcome.…”

“…40 It is reported that the degree of IL-1b production depends on the allelic interaction between the À511 and À31 polymorphic sites that determines the overall strength of IL-1b promoter. 32 Also a previous study revealed that high level of IL-1b in blood plasma is associated with IL-1b À511TT and À31CC genotype. 41 According to Tanaka et al (2003) IL-1b À511 proinflammatory TT genotype might be a factor for higher incidence of HCV associated HCC in Japanese population.…”

Interleukin 1 and Interleukin 4 Genes Polymorphism Associated With Early and Preschool Age Children Sensitization to Streptococcus Pyogenes

“…Показано, что гомозиготность и гетерозиготность индивидуумов по Т-аллелю IL1B*(+3953, С→T) связана с увеличенной продукцией белка IL-1β моноцитами крови в сравнении с индивидуумами, гомозигот-ными по С-аллелю [8,12,13,24]. Генотипы IL1B*(+3953, С→T)*T,T и C,T относят к высоко-продуцирующим вариантам гена IL1B.…”

Association of interleukin-1β -511C/T promoter polymorphism with COPD risk: a meta-analysis

“…However, although the contribution of the IL-1β -511C/T polymorphism to the IL-1β protein level has been observed in various diseases (Al-Tahhan et al, 2011;Olsson et al, 2012), there are no data regarding the correlation of genotypes of IL-1β -511C/T and IL-1β protein level in COPD. The haplotype of the IL-1β gene may have larger effects on IL-1β protein expression than does a single polymorphism (Chakravorty et al, 2006), but only 3 included studies conducted haplotype analysis of the IL-1β gene (Hegab et al, 2005;Lee et al, 2008;Trajkov et al, 2009), limiting further analysis.…”