Special Lecture : VEGF; Hot Track To Qualified Ulcer Healing

다국어 초록 (Multilingual Abstract)

Background and Aim: Irrespective of etiologies of peptic ulcer diseases (PUD), the most ulcers develop on the lesser curvature side of stomach including incisura and anterior wall of duodenal bulb. However, still no clear explanation why ulcers are prevalent in these areas has been given except some speculations including insufficient perfusion through abnormality in blood vessel, weak structural points or host characteristics. Here, we hypothesized that VEGF polymorphism can predict the susceptibility to peptic ulcer disease through deranged angiogenic activities. Methods: Based on several single nucleotide polymorphisms (SNPs) of vascular endothelial growth factor (VEGF) gene reported in literature search and their frequency studies done with Korean population, we performed the case-control study of 864 patients of chronic gastritis and gastric ulcer in 10 SNPs of VEGF gene including -2488 C/T, -634G/C, -7C/T, 3436G/C, 6112C/A, 6894C/T, 9374G/A, 9812C/T, 13128C/T, and 13553C/T, but of which results showed no statistically significant association between chronic gastritis and gastric ulcer. Results: We performed denatured high-performance liquid chromatography analysis to discover the novel SNP of VEGF gene, after which two novel SNPs of VEGF gene, -1780T/C and IVS-99 G/C, were identified, among which -1780T/C showed significant association between chronic gastritis and peptic ulcer disease, showing OR=2.93 on co-dominant analysis (p<0.001), OR=8.62 on dominant analysis (p<0.001), and OR=3.21 on recessive analysis (p<0.001). Promoter assay using site directed mutagenesis and in vitro angiogenesis assay showed repressed transcription of VEGF gene in gastric epithelial cells and defective tube formation in endothelial cells transfected with plasmid containing -1780C/C mutant of VEGF gene. Conclusion: Novel VEGF polymorphism, -1780T/C, is significantly associated with the predisposition to PUD after the exposure to etiologic risks.