Genetic polymorphisms in genes encoding antioxidant enzymes are associated with diabetic retinopathy in type 1 diabetes
Hovnik, Tinka ...
OBJECTIVE: Oxidative stress plays an important role in the development of microangiopathic complications in type 1 diabetes. We investigated polymorphicmarkers in genes encoding enzymes regulating ...production of reactiveoxygen species in association with diabetic retinopathy or diabetic nephropathy. RESEARCH DESIGN AND METHODS: A total of 124 patients with type 1 diabetes were investigated in this case-control study. All subjects were matched for sex, age, and duration of diabetes. Genotyping was conducted using real-time PCR for p.Val16Ala polymorphism in the MnSOD gene and c.C-262Tin the promoter region of the CAT gene. Multiplex PCR method was usedfor determination of GSTM1 and GSTT1 polymorphic deletions. Fluorescence-labeled PCR amplicons and fragment analysis was used for assessing the number of pentanucleotide (CCTTT)n repeats in inducible nitric oxide synthase. RESULTS: A positive association of MnSOD genotype Val/Val (odds ratio šORđ 2.49, 95% CI 1.00-6.16, P = 0.045) and GSTM1-1 genotype (2.63, 1.07-6.47, P = 0.031) with diabetic retinopathy but not with diabetic nephropathy was demonstrated. Additionally, the combination of the two genotypes conveyed an even higher risk (4.24, 1.37-13.40, P = 0.009). No otherinvestigated genetic polymorphisms were associated with either diabetic retinopathy or diabetic nephropathy. CONCLUSIONS: Selected polymorphisms in genes encoding MnSOD and GSTM1 could be added to a panel of genetic markers for identification of individuals with type 1 diabetes at an increased risk for developing diabetic retinopathy.
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