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

Cheng Chan Lu, Bor Shyang Sheu, Ten Wen Chen, Hsiao Bai Yang, Kuey Hsian Hung, Ai Wen Kao, Chiao Hsiung Chuang, Jiunn Jong Wu

Research output: Contribution to journalArticle

38 Citations (Scopus)

Abstract

OBJECTIVES: This study tested whether host genotypes of the tumor necrosis factor-alpha (TNF-α) 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-α 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-α expressions were stained by immunohistochemistry. RESULTS: In H. pylori-infected patients, -1031C or -863A carriers of TNF-α promoter had more severe gastric neutrophil infiltration and TNF-α 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 ≤ 0.00001) for the carriers with either -1031C or -863A allele, and even elevated to 6.06 (95% CI: 3.57-10.21, p ≤ 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 ≤ 0.005). CONCLUSIONS: TNF-α -1031 and -863 promoter SNP should be novel host factors to determine the gastric inflammation and risk of peptic ulceration upon H. pylori infection.

Original languageEnglish
Pages (from-to)1274-1282
Number of pages9
JournalAmerican Journal of Gastroenterology
Volume100
Issue number6
DOIs
Publication statusPublished - 2005 Jun 1

All Science Journal Classification (ASJC) codes

  • Hepatology
  • Gastroenterology

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