Association analysis of genetic variations of eNOS and α2ß1 integrin genes with type 2 diabetic retinopathy

Background: Diabetic retinopathy (DR) is classically defined as a microvasculopathy that primarily affects the small blood vessels of the inner retina as a complication of diabetes mellitus. It has been suggested that nitric oxide (NO) and α2β1 integrin (a platelet receptor for collagen) play an important role in the pathogenesis of microvascular complications in DR. Aim: The aim of this study was to investigate the association of two candidate genes involved in the regulation of retinal vasculature, endothelial nitric oxide synthase (eNOS) and α2β1 integrin (ITGA2) genes, with the development of DR in Egyptian patients with type 2 diabetes mellitus and to investigate whether genetic variants will affect the type of retinopathy (proliferative or nonproliferative). Methods: In this study, 70 patients were enrolled and categorized into two groups: (1) a DR group consisting of 50 patients with DR, which was further subclassified into 25 patients with nonproliferative DR (NPDR group) and 25 patients with proliferative DR (PDR group) and (2) a diabetes without retinopathy (DWR) group, comprising 20 patients with type 2 diabetes of more than 10 years' duration who showed no signs of DR. Associations of the genetic polymorphisms of eNOS (G894T) and ITGA2 (BgI II) were studied. Polymerase chain reaction-restriction fragment length polymorphism analysis was performed for all samples to evaluate the genotypes and correlate with the phenotype of the disease. Results: The allele frequencies of both polymorphisms showed considerable differences between patients with and without DR. The GG genotype of G894T polymorphism of eNOS was associated with a 9.75-fold increased risk of DR (95% confidence interval 1.7–55.4) and the genotype ITGA2 BgI II (+/+) was associated with a 10.1-fold increased risk of DR (95% confidence interval 1.8–57.9), while the α2β1 integrin gene polymorphism of genotype distribution of both eNOS and ITGA2 polymorphisms did not differ significantly between the proliferative and nonproliferative DR groups. Conclusion: A significant association between the G894T polymorphism of eNOS and BgI II polymorphism of ITGA2 genes and DR was observed, while there was no association between the genetic variants of those two polymorphisms and the type of retinopathy.