Abstract
Purpose: :
To establish a correlation between phenotypes of diabetic retinopathy progression (phenotypes I, II and III) and genotypes, as identified for 7 candidates genes, i.e. ALR, RAGE, VEGF, ICAM-1, TNF-a, ACE, and NOS-1 in a population of type 2 diabetic patients with non-proliferative diabetic retinopathy (NPDR).
Methods: :
Using non-invasive methods, as Color Fundus Photography (CFP) and Optical Coherence Tomography (OCT) to evaluate respectively, Microaneurysm Formation Rate (MAFR) and Retinal Thickness (RT), a population of 350 diabetic patients with NPDR was classified in 3 different phenotypes of DR progression:- Phenotype 1: MAFR ≤ 2 and Normal RT;- Phenotype 2: MAFR ≤ 2 and Increased RT;- Phenotype 3: MAFR >2.Each patient was submitted to genetic evaluation to identify different genes from a list of candidate genes classified based on gene organization and Single Nucleotide Polymorphisms (SNPs) density, as ALR, RAGE,VEGF, ICAM-1, TNF-a, NOS-1 and ACE. The distribution for each genotype and each allele (computed from the observed number of genotypes) were analyzed for the 3 different phenotypes.
Results: :
The preliminary results based in the first 98 patients showed a distribution of the 3phenotypes in this population of 40%, 26% and 34%, respectively for phenotypes1, 2 and 3. No statistically significant differences were found on genetic analysis eventually due to the small number of cases. Nevertheless, some genes showed interesting differences between phenotypes, although not statistically significant, i.e.: ICAM1_rs1801714 (P=0,082);NOS1_rs9658445 (P=0,469), AGER_rs1800625 (P=0,431).
Conclusions: :
Although no statistically significant differences were found so far, these preliminary results suggest the possibility that some genes are associated with different rates of progression of diabetic retinopathy in type 2 diabetic patients,therefore opening new perspectives for the management and the treatment of DR.
Clinical Trial: :
http://www.clinicaltrials.gov NCT01228981
Keywords: diabetic retinopathy • gene mapping • genetics