title: Transcriptional regulation of the VEGF gene in dependence of individual genomic variations.
abstract: Overexpression of the vascular endothelial growth factor (VEGF) gene has been associated with advanced stage and poor survival in several cancers. The majority of disease-associated VEGF-single nucleotide polymorphisms (SNPs) locate within regulatory regions. Therefore, an influence of SNPs located in the promoter/5'-untranslated region (5'UTR) on transcription factor binding (TFB) and gene expression seems feasible. We reviewed the literature investigating a potential connection of VEGF-SNPs and transcriptional regulation of the VEGF gene. In addition, we employed transcription factor databases to search for VEGF-SNPs which have already been associated with diseases. The objective of this review is to gain an overview about an association of VEGF-SNPs and the transcription factor dependent regulation of the VEGF gene. A decreasing binding specificity of the transcription factor MZF1 in presence of the VEGF-SNP +405 C-allele has been reported. TF databases indicated a potential HIF binding site for the -2578 C-allele representing an important potential inducer of VEGF expression. Additionally, linkage disequilibrium of the -2578 A-allele and an 18 bp insertion increases the number of potential TFB sites. For the VEGF promoter SNP -1154 A/G an interaction with the HRE under participation of the SNP +405 C/G was supposed. The comprehension of the association of specific SNPs and TFB could be an essential part in our understanding of individual differences of VEGF regulation and course of diseases.
authors.affiliation: Department of Otorhinolaryngology, University Medical Centre Mainz, Langenbeckstr. 1, 55101 Mainz, Germany.
authors.forename: Carmen S
authors.initials: CS
authors.lastname: Metzger
authors.affiliation: Department of Otorhinolaryngology, University Medical Centre Mainz, Langenbeckstr. 1, 55101 Mainz, Germany.
authors.forename: Dimitrios
authors.initials: D
authors.lastname: Koutsimpelas
authors.affiliation: Department of Otorhinolaryngology, University Medical Centre Mainz, Langenbeckstr. 1, 55101 Mainz, Germany. Electronic address: juergen.brieger@unimedizin-mainz.de.
authors.forename: Juergen
authors.initials: J
authors.lastname: Brieger
mesh_terms: D020121:5' Untranslated Regions; D005786:Gene Expression Regulation; D006801:Humans; D020641:Polymorphism, Single Nucleotide; D014158:Transcription, Genetic; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics*
chemical_list: D020121:5' Untranslated Regions; D042461:Vascular Endothelial Growth Factor A
keywords: Review; SNP; Transcriptional regulation; VEGF; Vascular endothelial growth factor