Abstract | BACKGROUND AND AIM: The gastroduodenal ulcer (GDU) mostly develops on the lesser curvature side of stomach and the anterior wall of duodenal bulb, irrespective of the etiologies including Helicobacter pylori infection, non-steroidal anti-inflammatory drugs, alcohol, etc. However, a clear explanation as to why ulcers are prevalent in these areas has still not been given. The current study was designed to evaluate whether the vascular endothelial growth factor ( VEGF) polymorphism could predict susceptibility to GDU through deranged angiogenic activities. METHODS: A large scale case-control study based on known single nucleotide polymorphisms (SNP) of VEGF and another case control study based on the novel SNP of VEGF was performed through the SNP-IT assay using the SNP stream 25 k system. A site-directed mutagenesis and functional assay was executed to document the biological effect of a novel VEGF SNP on angiogenesis. RESULTS: Even though the case-control study between non- ulcer dyspepsia (NUD) and gastric ulcer (GU) patients was done in 10 SNP of the VEGF gene including -2488C/T, -634G/C, -7C/T, 3436G/C, 6112C/A, 6894C/T, 9374G/A, 9812C/T, 13128C/T, and 13553C/T, the analysis showed no statistically significant association between NUD and GU. Denaturing high-performance liquid chromatography analysis could identify two novel SNP of the VEGF gene, -1780T/C and IVS-99 G/C, among which -1780T/C showed a very strong association between NUD and GDU, presenting with OR=2.93 on codominant analysis (P<0.001), OR=8.62 on dominant analysis (P<0.001), and OR=3.21 on recessive analysis (P<0.001). The promoter assay using a site-directed mutagenesis and in vitro angiogenesis assay showed repressed transcription of the VEGF gene in gastric epithelial cells and defective tube formation in endothelial cells, both transfected with a plasmid containing -1780C/C mutant of VEGF gene. CONCLUSION: The novel VEGF polymorphism -1780T/C could significantly predict the predisposition to GDU after the exposure to etiologic risks, based on defective angiogenic activity.
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Authors | Yong Seok Kim, Sang Woon Park, Min Ho Kim, Eun Jeong Jang, Ju Sang Park, Sang Jong Park, Hyun Wook Baik, Gregory Chung, Ki Baik Hahm |
Journal | Journal of gastroenterology and hepatology
(J Gastroenterol Hepatol)
Vol. 23 Suppl 2
Pg. S131-9
(Dec 2008)
ISSN: 1440-1746 [Electronic] Australia |
PMID | 19120886
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- VEGFA protein, human
- Vascular Endothelial Growth Factor A
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Topics |
- Adolescent
- Adult
- Aged
- Aged, 80 and over
- Case-Control Studies
- Cells, Cultured
- Child
- Duodenal Ulcer
(genetics, metabolism, physiopathology)
- Endothelial Cells
(metabolism)
- Female
- Genetic Predisposition to Disease
- Humans
- Male
- Middle Aged
- Mutagenesis, Site-Directed
- Neovascularization, Physiologic
(genetics)
- Odds Ratio
- Polymorphism, Single Nucleotide
- Promoter Regions, Genetic
- Risk Assessment
- Risk Factors
- Stomach Ulcer
(genetics, metabolism, physiopathology)
- Transcription, Genetic
- Transfection
- Vascular Endothelial Growth Factor A
(genetics, metabolism)
- Young Adult
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