Role of host interleukin 1beta gene (IL-1B) and interleukin 1 receptor antagonist gene (IL-1RN) polymorphisms in clinical outcomes in Helicobacter pylori-positive Turkish patients with dyspepsia

J Gastroenterol. 2008;43(9):705-10. doi: 10.1007/s00535-008-2220-7. Epub 2008 Sep 20.

Abstract

Background: Helicobacter pylori infection leads to different clinical outcomes depending on both host and bacterial factors. In a recent study, we identified H. pylori cagE and babA2 genotypes as independent predictors of duodenal ulcer (DU) and gastric cancer (GC) in dyspepsia patients, but no previous studies have examined the role of host-related genetic factors in Turkey. This time our aim was to evaluate whether polymorphisms of the interleukin 1B (IL-1B) and the interleukin 1 receptor antagonist (IL-1RN) genes are important factors in the differential expression of gastroduodenal diseases in H. pylori-positive dyspepsia patients.

Methods: Ninety-three H. pylori-positive patients, 30 with nonulcer dyspepsia (NUD), 30 with DU, and 33 with GC, were investigated. The IL-1B-511 and IL-1B-31 biallelic polymorphisms, and the IL-1RN intron 2 variable number tandem repeat were genotyped by polymerase chain reaction and single-strand confirmation polymorphism analysis.

Results: The IL-1RN-1/1 genotype was significantly more prevalent among patients with NUD than among those with GC (chi(2) = 9.270; P = 0.002), and the IL-1RN-1/2 genotype was significantly more common in patients with GC (chi(2) = 6.01; P = 0.014). Multivariate regression analysis showed that cagE, babA2, and IL-1RN-1/2 genotypes were independent predictors of GC, but when patients with benign disorders were grouped together (NUD + DU) and compared with patients with GC, regression analysis disclosed that babA2 (P = 0.000) and IL-1B-31 gene polymorphisms (CC or CT) (P = 0.01) were the only independent markers of GC.

Conclusions: When analyzed together with host genetic factors, the well established bacterial risk factor babA2 seems to be the most important predictor of malignant disorders, and the presence of the IL-1B-31TT genotype emerges as a protective factor against them.

MeSH terms

  • Adhesins, Bacterial / metabolism
  • Adult
  • Aged
  • Aged, 80 and over
  • Antigens, Bacterial / metabolism
  • Bacterial Proteins / metabolism
  • Duodenal Ulcer / etiology
  • Duodenal Ulcer / genetics
  • Dyspepsia / genetics*
  • Dyspepsia / microbiology
  • Female
  • Genotype
  • Helicobacter Infections / complications*
  • Helicobacter pylori* / metabolism
  • Humans
  • Interleukin 1 Receptor Antagonist Protein / genetics*
  • Interleukin-1beta / genetics*
  • Male
  • Middle Aged
  • Polymorphism, Genetic*
  • Stomach Neoplasms / etiology
  • Stomach Neoplasms / genetics

Substances

  • Adhesins, Bacterial
  • Antigens, Bacterial
  • BabA protein, Helicobacter pylori
  • Bacterial Proteins
  • Interleukin 1 Receptor Antagonist Protein
  • Interleukin-1beta
  • cagA protein, Helicobacter pylori