Fig. 2.

SNPs affecting expression of genes in the VEGF signalling pathway. Green boxes denote increased, whereas red boxes denote reduced expression of the respective protein levels or function. The A allele of the two coding VEGFR-2 SNPs, i.e. rs2305948 and rs1870377, induces a valine to isoleucine and histidine to glutamine substitution, respectively, at positions 297 and 472, thereby reducing the affinity for VEGF. In HIF-1α, the T allele of rs11549465 induces a proline to serine substitution at position 582, and the A allele in rs11549467 induces an alanine to threonine substitution at position 588, thereby increasing HIF-1α stability. PHD, prolyl hydroxylation domain protein; VHL, von Hippel-Lindau protein; HIF, hypoxia inducible factor; VEGF-A, vascular endothelial growth factor-A; VEGFR, VEGF receptor.