Original Article
The American Journal of Gastroenterology (2005) 100, 1274–1282; doi:10.1111/j.1572-0241.2005.40852.x
Host TNF-
-1031 and -863 Promoter Single Nucleotide Polymorphisms Determine the Risk of Benign Ulceration after H. pylori Infection
Cheng-Chan Lu PhD1, Bor-Shyang Sheu MD1, Ten-Wen Chen MS1, Hsiao-Bai Yang MD1, Kuey-Hsian Hung PhD1, Ai-Wen Kao MD1, Chiao-Hsiung Chuang MD1 and Jiunn-Jong Wu PhD1
1Departments of Internal Medicine, Pathology, and Medical Technology, Institute of Microbiology and Immunology and Institute of Basic Medicine, Medical College, National Cheng Kung University, Tainan, Taiwan
Correspondence: Bor-Shyang Sheu, MD, Department of Internal Medicine, National Cheng Kung University Hospital, 138 Sheng Li Road, Tainan 704, Taiwan
Received 26 May 2004; Revised 0000; Accepted 8 December 2004.
Abstract
OBJECTIVES:
This study tested whether host genotypes of the tumor necrosis factor-alpha (TNF-
) 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- 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- expressions were stained by immunohistochemistry.
RESULTS:
In H. pylori-infected patients, -1031C or -863A carriers of TNF- promoter had more severe gastric neutrophil infiltration and TNF- 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--1031 and -863 promoter SNP should be novel host factors to determine the gastric inflammation and risk of peptic ulceration upon H. pylori infection.
