Association between E-selectin S128R (A561C) polymorphism and diabetic retinopathy ( a possible relationship)

Abstract

Background E-selectin is a cell surface glycoprotein that mediates the adhesion of leukocytes to the vessel endothelium. Diabetic retinopathy, a leading cause of vision loss, is associated with altered endothelial function. Endothelial dysfunction, such as that in diabetes, is associated with altered production of leukocyte-adhesive molecules, for example, E-selectin. However, it is unknown whether genetic polymorphism in the E-selectin gene plays a role in diabetic retinopathy. This is a case–control study to determine the frequencies of E-selectin genotypes and allelic forms in diabetic patients having diabetic retinopathy and to evaluate the role of E-selectin gene polymorphism as a predisposing factor for diabetic retinopathy. E-selectin polymorphism was determined in 84 type 2 diabetic patients and in 40 age-matched and sex-matched controls. In the diabetic group, 46 patients had no retinopathy, whereas the other 38 were duration-matched diabetic patients with diabetic retinopathy. E-selectin genotyping was accomplished by PCR amplification, followed by restriction enzyme digestion (restriction fragment length polymorphism). The E-selectin level in plasma was estimated using the enzyme-linked immunosorbent assay (ELISA). In addition, the lipid profile was determined using the colorimetric method. Results In the present case–control study, a total of 85% of controls had the AA genotype, whereas 15% had the AC genotype; the CC genotype was not detected. Frequencies of the AA, CC, and AC genotypes were found to be 37, 32.6, and 30.4% in diabetic patients with no retinopathy and 31.6, 36.8, and 31.6% in diabetic patients with retinopathy respectively. The CC genotype was significantly associated with diabetic patients as a whole (odds ratio: 6.9, 95% confidence interval: 2.2–21.6; P =0.0001), but no genotype was associated significantly with diabetic retinopathy patients. All lipid profile parameters and plasma levels of E-selectin were significantly increased in diabetic patients; however, high-density lipoprotein cholesterol was significantly reduced in the diabetic patient group as a whole as well as in the diabetic retinopathy patient group. Conclusion The S128R (A561C) polymorphism of the E-selectin gene may be associated with diabetes mellitus but not with diabetic retinopathy, suggesting that the E-selectin gene polymorphism has no role as a predisposing factor for diabetic retinopathy. Such a hypothesis needs to be further confirmed by larger studies.