Study On The Relationship Between Polymorphism Of Manganese Superoide Dismutase Gene And Diabetic Microvascular Complications In Type 2 Diabetes Mellitus

Objectives:Diabetes,along with it's chronic complication ,is severly threatening diabetic patients' health .Most recently studies indicated that Oxidative stress may be play an important role as a initiative event during various pathogenesis of diabetic chronic complication .Mn-SOD ,as an important antioxidant enzyme in mitochondria, was paid more attention. A C to T substitution at position 1183 in human Mn-SOD gene has been shown to change the secondary structural conformation of the mitochondrial targeting sequence of the enzyme coded by Mn-SOD gene, followed by change in Mn-SOD content in the mitochondria. Our study aimed at investigate the relationship between the C1183T polymorphism of Mn-SOD gene and diabetic microangiopathy in the Han Nationality peoples of North of China. Methods:Randomly recruited 232 inpatients with type 2 diabetes mellitus and 96 non-diabetes subjects, and collected their clinical data. Total genome was extracted in peripheral blood. PCR-RFLP techniques were performed to screen the mutation of C1183T in human Mn-SOD gene. The differences of frequency in alleles and genotypes were compaired among groups. Results:(1) A polymorphism Cl 183T was discovered both in type 2 diabetes mellitus and controls, and no difference between two groups for the frequence of C allele, Tallele,and the C/C,C/T,T/T genotypes were found(2) In type 2 diabetes mellitus with overt nephropathy, a increased frequency of T/T genotype was found in comparison with type 2 diabetes mellitus without nephropathy, however, compaired with early diabetic nephropathy, no difference was found. Between type 2 diabetes mellitus without nephropathy and early diabetic nephropathy, no difference was also found. The frequency of allel was no difference among groups.(3) The frequency of allel and genotype was no difference among type 2 diabetes mellitus without retinopathy, and with backgrond diabetic retinopathy and preliferative diabetic retinopathy. However, with progression of retinopathy, the frequency of T/T genotype trend toward increasing among groups.(4) A increased frequency of T/T genotype and T allel was found in DN(+)/DR(+) compared with DN (-) /DR (+) group or DN (+) /DR (-) group, but compared with DN (-) /DR (-) group,no difference was found.(5) Logistic regression analysis was done to assess the relationship between progression of nephropathy from normoalbuminuria to macroalbuminuria and the risk factors of nephropathy and Mn-SOD genotype. Results indicated that genotype of Mn-SOD body mass index, SBPand CR were significantly associated with nephropathy.Conclusion:(1) The polymorphism C1183T of human Mn-SOD gene has two types allel (C, T) and three types genotype (C/CUC7I\ T/T).(2) The polymorphism may be unrelated to the etiology of type 2 diabetesmellitus(3) The polymorphism C1183T of human Mn-SOD gene seems to be associated with diabetic nephropathy; is a independent risk factor of diabetic nephropathy; The T/T genotype may be a risk factor contributed to the progression of nephropathy.(4) The polymorphism has no association with diabetic retinopathy, However , with progression of retinopathy, the frequency of T/T genotype trend toward increasing in groups.(5) when accompanied with nephropathy and retinopathy simultaneously, the role of T/T genotype in the progression of diabetic microangiopathy was hanced...