Association of candidate genes (ALR2, RAGE, and VEGF) polymorphisms with diabetic retinopathy in type 2 diabetic patients in Khyber Pakhtunkhwa, Pakistan

Abstract

Abstract AIM: To evaluate the aldose reductase (ALR2, rs759853), receptor for advanced glycation end products (RAGE, rs2070600), and vascular endothelial growth factor (VEGF, rs833061) association with diabetic retinopathy in type 2 diabetic patients in Khyber Pakhtunkhwa population.Methods: A Case control study was conducted on a total of 550 subjects consisting of 186 with diabetic retinopathy (DR) having type 2 diabetes, 180 had type 2 diabetes (T2DM), and 184 healthy controls (HC). All the samples were subjected to DNA isolation using salting-out method followed by SNP genotyping through Tetra-ARMS PCR. Chi square and Exact Fischer tests were used for allele and genotype distribution. Odd ratio and confidence interval values were found out by online software Medcalc Odd ratio Calculator.Results: Multiple parameters such as random blood sugar (RBS) (p<0.001), fasting blood sugar (FBS) (p<0.001), HbA1c (p<0.001), total cholesterol (p<0.001), LDL (p<0.001), HDL (p<0.001), BMI (p<0.001) and hypertension (p=0.018) showed strong association with DR as compared to DM and HC. Our results showed that VEGF rs833061 (p<.001) and RAGE rs2070600 (p<.001) polymorphism was strongly associated with an increased risk of DR. The odd ratio of CC genotype in VEGF (0.262, 95% CI=0.129-0.531) and AA genotype in RAGE (0.59, 95% CI=0.032-0.110) was noted. However, the significance in ALR2 rs759853 gene polymorphism was observed at (p=0.001). Conclusion: There is a statistically significant association of VEGF rs833061 and RAGE rs2070600 with diabetic retinopathy in type 2 diabetic patients. Also, this is the first study to report the association of RAGE with diabetic retinopathy in type 2 diabetes in Khyber Pakhtunkhwa population.