To provide a more precise evaluation of the association between the (CA)n variations of ALR and the risk for DR, a meta-analysis was performed in the present study.
This review critically analyses different treatments available for diabetic retinopathy, their limitations and the importance of the development of novel inhibitors of ALR2 that could prevent progression of DR, by causing a direct or indirect effect on controlling factors associated with DR.
Aldose reductase (AR) is an NADPH-dependent aldo-keto reductase that has been shown to be involved in the pathogenesis of several blinding diseases such as uveitis, diabetic retinopathy (DR) and cataract.
RESULTS We found that variants of ALR2rs759853 polymorphism were significantly associated with an increased risk of diabetic retinopathy, whereas variants of SDH rs2055858 polymorphism were significantly associated with a lower risk.
Aldose reductase (ALR), the first and rate-limiting enzyme involved in polyol pathway plays a central role in diabetes and its related complications, including diabetic retinopathy (DR).
Association of the Aldose Reductase-106TT Genotype with Increased Risk for Diabetic Retinopathy in the Chinese Han Population: An Updated Meta-Analysis.
The gene coding for vascular endothelial growth factor, aldose reductase, and the receptor for advanced glycation end products have been extensively evaluated, and specific polymorphisms of these genes have been suggested to potentially increase the risk of DR development.
The accelerated polyol pathway triggers a cascade of events leading to retinal vascular endothelial dysfunction and the eventual development of DR. Polymorphisms in the gene encoding aldose reductase have been consistently associated with DR.
Z+2 allele of ALR2, 13-repeat genotype of iNOS, 15-repeat genotype of TNF-β, genes were associated with susceptibility to DR. Gly82Ser polymorphisms of the RAGE gene were not associated with DR in the present study.
The T allele of the AKR1B1 promoter rs759853 variant is also significantly protective against diabetic retinopathy in type 1 diabetes (0.5 [0.35-0.71], P = 1.00 x 10(-4)), regardless of ethnicity.
These results imply that methods designed to normalize aldose reductase and nitric oxide synthase activities could be of significant benefit in the prevention and treatment of diabetic retinopathy.
Levels of ALR2 activity as well as sorbitol in erythrocytes may have value as a quantitative trait to be included among other markers to establish a risk profile for development of DR.
The aim of this study was to investigate the relationship between the AC(n) repeat and C(-106)T polymorphisms of the ALR2 gene with the susceptibility to the development of DR in Brazilian patients with type 1 diabetes.
To further test the possible pathogenic role of aldose reductase in the development of diabetic retinopathy, we examined the retinal effects of this structurally novel and highly selective ARI in insulinized streptozotocin-induced diabetic rats.
Thus, our results show that the -106CC genotype (-106C>T polymorphism) in the AR gene is related to the progression of diabetic retinopathy in Caucasian-Brazilians with type 2 diabetes.
Variants in the aldose reductase gene (AKR1B1) have been implicated in the development of diabetic retinopathy and nephropathy, with the most convincing data identifying a (CA)(n) repeat microsatellite allele (Z-2), which has a functional role in gene expression.
Our results suggest that the Z-2 allele of the aldose reductase gene is a risk factor for the development of diabetic retinopathy in a group of Caucasian participants with Type 2 diabetes.