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 afterHelicobacter pyloriinfection.METHODS: A total of 524 dyspeptic patients, 424 with and 100 withoutH. pyloriinfection, were checked forTNF-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 detectH. pyloriinfection and its related histology using the updated Sydney's system. Gastric TNF-α expressions were stained by immunohistochemistry.RESULTS: InH. pylori-infected patients,−1031C or−863A carriers ofTNF-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 theH. pylori-infected hosts (p<0.05). As compared to−863CC and−1031TT genotype combinations, the ulcer risk afterH. pyloriinfection 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 uponH. pyloriinfection.(Am J Gastroenterol 2005;100:1–9) [ABSTRACT FROM AUTHOR]