Evaluation of AC(n) and C(-106)T polymorphisms of the aldose reductase gene in Brazilian patients with DM1 and susceptibility to diabetic retinopathy

Diabetic retinopathy (DR) is one of the most important microvascular complications in both type 1 and type 2 diabetes. In Brazil, its proliferative form is the second cause of irreversible blindness among adults of working age. Despite the strong association of DR with disease duration and degree of chronic hyperglycemia, genetic predisposition has been recognized as a possible trigger in the development of this complication. Recent studies have demonstrated that the development of DR in patients with type 1 diabetes is associated with the occurrence of polymorphisms at the 5'-end of the aldose reductase gene (ALR2). There are no reports investigating these polymorphisms in type 1 diabetes Brazilian patients. 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. We selected 64 patients who had diabetes for at least 10 years from Santa Casa de São Paulo and State University of Campinas. The study group was divided into the following: Group 1, patients with no evidence of diabetic retinopathy; group 2, patients with nonproliferative diabetic retinopathy (NPDR); and group 3, patients with proliferative diabetic retinopathy (PDR), confirmed by fundoscopy. The AC(n) microsatellite region was evaluated through polymerase chain reaction (PCR) and automated genotyping and the C(-106)T substitution through polymerase chain reaction/restriction fragment length polymorphism (RFLP). When each allele of the AC(n) polymorphism was evaluated, the Z allele (24 repeats) was significantly associated with the development of PDR (p=0.014). The C allele of the C(-106)T substitution wasn't associated with the susceptibility to this microvascular complication (p=0.153). When the Z and C allele were concomitantly evaluated regarding their presence or absence a positive correlation was observed for the presence of both alleles and the development of PDR. In our sample of Brazilian patients with type 1 diabetes, the presence of the AC(n) polymorphism Z allele may be considered a risk factor for the development of PDR. The C allele of the C(-106)T polymorphism, in association with the Z allele, also increased the risk for the development of PDR, but when it was analyzed by itself there was no association with the complication.