Host TNF-alpha-1031 and -863 promoter single nucleotide polymorphisms determine the risk of benign ulceration after H. pylori infection.
OBJECTIVE
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.
Lu
Cheng-Chan
CC
Department of Internal Medicine, Institute of Microbiology and Immunology and Institute of Basic Medicine, Medical College, National Cheng Kung University, Tainan, Taiwan.
Sheu
Bor-Shyang
BS
Chen
Ten-Wen
TW
Yang
Hsiao-Bai
HB
Hung
Kuey-Hsian
KH
Kao
Ai-Wen
AW
Chuang
Chiao-Hsiung
CH
Wu
Jiunn-Jong
JJ
D001706:Biopsy; D004247:DNA / Q000235:genetics*; D004381:Duodenal Ulcer / Q000209:etiology / Q000378:metabolism / Q000473:pathology; D016145:Endoscopy, Digestive System; D005260:Female; D005753:Gastric Mucosa / Q000378:metabolism* / Q000382:microbiology / Q000473:pathology; D005786:Gene Expression Regulation / Q000502:physiology; D005819:Genetic Markers; D005838:Genotype; D016481:Helicobacter Infections / Q000150:complications* / Q000378:metabolism / Q000473:pathology; D016480:Helicobacter pylori / Q000302:isolation & purification; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D009504:Neutrophils / Q000473:pathology; D016133:Polymerase Chain Reaction; D020641:Polymorphism, Single Nucleotide; D011401:Promoter Regions, Genetic / Q000235:genetics*; D013276:Stomach Ulcer / Q000209:etiology* / Q000378:metabolism / Q000473:pathology; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics* / Q000378:metabolism
D005819:Genetic Markers; D014409:Tumor Necrosis Factor-alpha; D004247:DNA