Transcriptional regulation of the VEGF gene in dependence of individual genomic variations

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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.

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