Several candidate genes have been so far implicated in the pathogenesis of proliferative diabetic retinopathy (PDR) in subjects with type 2 diabetes. Since the principal pathogenetic mechanisms for diabetic retinopathy (DR) and PDR are different, the main pathogenetic mechanism in DR is increased vascular permeability, whereas in PDR the crucial pathogenetic mechanisms are fibrosis and neoangiogenesis. Due to that fact, different candidate genes are expected to be involved in the development of either DR or PDR. None of the candidate genes, however, can be fully and solely responsible for the development of PDR and for DR progression into PDR. Epigenetic mechanisms are expected to be involved in the pathogenesis of PDR as well. Gene polymorphisms responsible for PDR and epigenetic mechanisms responsible for PDR are reviewed in this paper.

Background: Many studies have reported increased serum levels of vascular endothelial growth factor (VEGF) in patients with acute coronary syndromes. We searched for the association between either the –634 C/G or the insertion/deletion (I/D) polymorphism of the VEGF gene and myocardial infarction (MI) in subjects with type 2 diabetes. Methods: 143 subjects with type 2 diabetes and MI were compared to 228 diabetic subjects without coronary artery disease (CAD). VEGF serum levels were analyzed in 94 subjects with type 2 diabetes without CAD. Results: A significantly higher frequency of the CC genotype of the –634 C/G VEGF polymorphism was found in the patients with MI compared to the patients without CAD (17.5 vs. 9.2%; p = 0.019), whereas the insertion/deletion VEGF polymorphism failed to yield an association with MI. Significantly higher VEGF serum levels were demonstrated in subjects with the CC genotype compared to those with the other (CG + GG) genotypes (60.4 ± 32.1 vs. 44.1 ± 23.5 ng/l; p < 0.01). Conclusions: The present study demonstrates that the CC genotype of the –634 C/G VEGF gene might be a risk factor for MI in Caucasians with type 2 diabetes of duration of more than 10 years.

Substantial data indicate that oxidative stress is involved in the development of diabetic retinopathy. Two candidate genes that affect the oxidative stress are manganese mitochondrial superoxide dismutase (Mn‐SOD) and endothelial nitric oxide synthase (eNOS). The aim of the present study was to examine the role of the V16A polymorphism of the Mn‐SOD gene and the 4a/b polymorphism of the eNOS gene in the development of diabetic retinopathy in Caucasians with type 2 diabetes.In this cross sectional case‐control study 426 unrelated Slovene subjects (Caucasians) with type 2 diabetes mellitus were enrolled: 283 patients with diabetic retinopathy and the control group of 143 subjects with type 2 diabetes of duration of more than 10 years who had no clinical signs of diabetic retinopathy.A significantly higher frequency of the VV genotype of the V16A polymorphism of the Mn‐SOD was found in patients with diabetic retinopathy compared to those without diabetic retinopathy (OR=2.1, 95% CI = 1.2–3.4; p = 0.006), whereas the 4a/b polymorphism of the eNOS gene failed to yield an association with diabetic retinopathy.We may conclude that the VV genotype of the V16A polymorphism of the Mn‐SOD gene was associated with diabetic retinopathy in Caucasians with type 2 diabetes, therefore it might be used as a genetic marker of diabetic retinopathy in Caucasians.