Scientific background:

Summary: Genetic variations in this gene correlate with diabetic retinopathy.

Gene: The gene coding vascular endothelial growth factor is about 16kb in size. It is located on chromosome 6 (6p12). The gene consists of 7 exons.

Molecule: The translational product of this gene forms a heterodimeric glycoprotein.

Pathology: The fact that elevated intraocular concentrations of vascular endothelial growth factor can be found in advance of clinical manifestation of diabetic retinopathy does support its pathogenetic role in diabetic retinopathy. Moreover a retinopathy like disease can be induced experimentally in nondiabetic animals by intraocular injections of this protein.

Pathophysiology: The vascular endothelial growth factor regulates angiogenesis and vascular permeability. This assertion is further underpinned by the observation that a drug (ranibizumab), a specific inhibitor of the protein, appears to be suitable for treatment of macula oedema associated with diabetic retinopathy.

Clinical signs: The diabetic retinopathy is the main cause for acquired blindness in developed countries. It is obvious that beside of environmental factors (quality of diabetes control and duration of diabetes) genetic factors influence clinical manifestation. This way the manifestation of retinopathy can be correlated to -634C-allel of VEGF gene. This mutation results in elevated plasma levels of the protein. An allel dosage can be observed. That means the risk of retinopathy increases with following genotypes GG, GC, CC.

Epidemiology: The frequencies of these genotypes are only reported in the Japanese population. They are for CC, CG and GG 10, 50 and 40% respectively.

Interpretation: The risk of diabetic retinopathy is elevated 3 times in CC-genotype.

Test strategy: The genetic test should not be considered before clinical manifestation of diabetes. The test can help to define the need and the schedule of diagnostic an therapeutic procedures. This is specially important in families with increased risk.

Methodology:

	research test	Method		Genomic sequencing of the entire coding region
		Turn-around time		25 working days
		Effort		25 working days
		Specimen		DNA
		Quality assessment		Internal quality control only
	All known and new missense, nonsense and splice mutations can be detected.
	research test	Method		Hotspot sequencing
		Turn-around time		25 working days
		Effort		little
		Specimen		DNA
		Quality assessment		Internal quality control only
	Only in the region of interest, known and new missense, nonsense and splice mutations can be detected.

Literature: 

Awata T et al. (2002) A common polymorphism in the 5'-untranslated region of the VEGF gene is associated with diabetic retinopathy in type 2 diabetes.
Ferrara N et al. (1997) The biology of vascular endothelial growth factor.
Duh E et al. (1999) Vascular endothelial growth factor and diabetes: the agonist versus antagonist paradox.
Nguyen QD et al. (2006) Vascular endothelial growth factor is a critical stimulus for diabetic macular edema.
Eremina V et al. (2004) The role of VEGF-A in glomerular development and function.