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  • Title: Host TNF-alpha-1031 and -863 promoter single nucleotide polymorphisms determine the risk of benign ulceration after H. pylori infection.
    Author: Lu CC, Sheu BS, Chen TW, Yang HB, Hung KH, Kao AW, Chuang CH, Wu JJ.
    Journal: Am J Gastroenterol; 2005 Jun; 100(6):1274-82. PubMed ID: 15929757.
    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.
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