Host TNF-alpha-1031 and -863 promoter single nucleotide polymorphisms determine the risk of benign ulceration after H. pylori infection

Am J Gastroenterol. 2005 Jun;100(6):1274-82. doi: 10.1111/j.1572-0241.2005.40852.x.

Abstract

Objectives: This study tested whether host genotypes of the tumor necrosis factor-alpha (TNF-alpha) promoter single nucleotide polymorphism (SNP) could determine clinical and histological outcomes after Helicobacter pylori infection.

Methods: A total of 524 dyspeptic patients, 424 with and 100 without H. pylori infection, were checked for TNF-alpha promoter SNP over the locus on -1031(T/C), -863(C/A), -857(C/T), -806(C/T), and -308(G/A) by sequence-specific oligonucleotide probe. Each patient received panendoscopy to take gastric biopsy to detect H. pylori infection and its related histology using the updated Sydney's system. Gastric TNF-alpha expressions were stained by immunohistochemistry.

Results: In H. pylori-infected patients, -1031C or -863A carriers of TNF-alpha promoter had more severe gastric neutrophil infiltration and TNF-alpha gastric staining than individuals with -1031TT or -863CC genotype, respectively (p<0.05). The multivariate logistic regression verified both -1031C and -863A carriers were independent risk factors to have duodenal ulcers and gastric ulcer without IM in the H. pylori-infected hosts (p<0.05). As compared to -863CC and -1031TT genotype combinations, the ulcer risk after H. pylori infection was 2.46 (95% CI: 1.32-4.59, p<or=0.00001) for the carriers with either -1031C or -863A allele, and even elevated to 6.06 (95% CI: 3.57-10.21, p<or=0.00001) for the individuals harboring both -863A and -1031C alleles. For patients with gastric ulcer, the 863CC genotype had a higher rate to have intestinal metaplasia than -863A carrier (p<or=0.005).

Conclusions: TNF-alpha-1031 and -863 promoter SNP should be novel host factors to determine the gastric inflammation and risk of peptic ulceration upon H. pylori infection.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Biopsy
  • DNA / genetics*
  • Duodenal Ulcer / etiology
  • Duodenal Ulcer / metabolism
  • Duodenal Ulcer / pathology
  • Endoscopy, Digestive System
  • Female
  • Gastric Mucosa / metabolism*
  • Gastric Mucosa / microbiology
  • Gastric Mucosa / pathology
  • Gene Expression Regulation / physiology
  • Genetic Markers
  • Genotype
  • Helicobacter Infections / complications*
  • Helicobacter Infections / metabolism
  • Helicobacter Infections / pathology
  • Helicobacter pylori / isolation & purification
  • Humans
  • Immunohistochemistry
  • Male
  • Middle Aged
  • Neutrophils / pathology
  • Polymerase Chain Reaction
  • Polymorphism, Single Nucleotide*
  • Promoter Regions, Genetic / genetics*
  • Stomach Ulcer / etiology*
  • Stomach Ulcer / metabolism
  • Stomach Ulcer / pathology
  • Tumor Necrosis Factor-alpha / genetics*
  • Tumor Necrosis Factor-alpha / metabolism

Substances

  • Genetic Markers
  • Tumor Necrosis Factor-alpha
  • DNA