Association of MnSOD-47C/TGENE Polymorphism (Rs 4880-47C/T) in Sudanese Patient with Diabetic Retinopathy

Background: Diabetic retinopathy (DR) is the common micro-vascular complication of diabetes mellitus (DM). 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 glutathione genes. The study aims to assess the role of manganese superoxide dismutase MnSOD (rs4880) gene polymorphism in diabetic retinopathy Sudanese patients and its relation with MnSOD level. In addition to determine the association of Fasting Blood Glucose (FBS), HbA1c and Lipid in the pathogenesis of diabetic retinopathy.

Methodology: The number of subject 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 – 80) years old, from Makkah Eye Complex. DNA was extracted and PCR product for MnSOD, gene segment was digested by NgoM enzymes, moreover gene polymorphisms were determined. Serum MnSOD, 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 more 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 MnSOD, 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 Diabetic without retinopathy (DNR).The genotyping for MnSOD-47C/T showed that the frequency of genotype CC was significantly lower in cases compared with control. Theses Associations for SNPs CCs, MnSOD-47C/T SNP rs4880, decreased risk after correction for multiple testing (OR = 0.088, 95% CI = 0.034-0.224 p= 0.001), While the frequency of the CT heterozygote genotype was significantly higher in cases group compare with control, the OR= 3.76(1.41-10.5), P=0.006. While frequency of the TT genotype was significantly higher in cases than controls. Theses Associations for MnSOD 47C/T SNP rs4880, increased risk after correction for multiple testing (OR = 5.31, 95% CI = 1.91-14.75, p= 0.001). The C allele is observed in 47% of the cases while the T allele – risky allele- observed in 73% of the cases, OR= 0.150(0.079-0.285), P=0.001 (Table 6).

Conclusion: The study concludes that there is a significant association between MnSOD-47C/T (rs 4880) gene polymorphism and the occurrence of diabetic retinopathy in Sudanese population. There is a significant decrease in MnSOD levels and glycemic control in patients with the mutant allele T.