Abstract
Background: Diabetic retinopathy is the common micro-vascular complication of diabetes mellitus. It is the main cause of blindness among young adults worldwide. Poor glycemic control in addition to longer diabetic duration is the main risk factors for diabetic retinopathy. Many genes have been postulated as candidates for diabetic retinopathy. Little is known about anti-oxidative enzyme gene polymorphism and its association with diabetic retinopathy, mainly for catalase enzyme and manganese superoxide dismutase and glutathone genes. The study aims to assess the role of glutathone GPX-198C/T (rs1050450) gene polymorphism in diabetic retinopathy Sudanese patients and its relation with GPX level. In addition to determine the association of FBS, HbA1c and lipid in the pathogenesis of diabetic retinopathy. Methodology: The number of subjects involved were 130 which were classified into (n 60) clinically diagnosed as diabetic retinopathy and (n 70) diabetes mellitus without retinopathy as control group, age ranged from 22 to 80 years old, from Makkah Eye Complex. DNA was extracted and PCR product for GPX, gene segment were digested by Aba1 enzymes, moreover gene polymorphisms were determined. Serum GPX, activity and FBS, TG, CHOL and HbA1c level were analyzed using Cobas Int 400 using absorption photometer and immunoassay methods respectively. Results: The results revealed that, retinopathy is common in female than male by approximately 2 fold =1.9:1. Type II is more common in our population that type 1. The majority of the patients had type II diabetes (128, 98.5%) and only 2(1.5%) patients were type I diabetes mellitus. The activity of GPX, was significantly higher in DNR when compared with DR (p=0.003). Mean HbA1c and FBG concentration were significantly higher among DR than DNR p=0.001 and p=0.001 respectively. In contrast, mean serum CHOL and TG level revealed insignificant differences when compared DR with DNR. The genotyping for GPX-198C/T showed that, the frequency of CC was observed in 33(47%) in control higher than cases 13(22%), theses Associations for CCs, GPX-198C/T SNP rs1050450, decreased risk after correction for multiple testing (OR=0.310, 95% CI=0.176-0.486, p=0.001), While TT genotype was detected in 25(42%) cases and only 14(20%) in controls, these Associations for SNPs, TTs, GPX-198C/T SNP rs1050450, increased risk after correction for multiple testing (OR=2.4, 95% CI=1.10-5.90, p=0.004). The frequency of the allele C protective allele was found to be 48% among cases group while allele T-risky allele was higher among cases group 72%, OR=0.357 (0.216-0.433), p=0.001. Conclusion:The study concludes that there is a significant association between GPX-198C/T (rs1050450) gene polymorphism and the occurrence of diabetic retinopathy in Sudanese population. There is a significant decrease in GPX levels and glycemic control in patients with the mutant allele T.
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