Genetic polymorphisms in genes encoding antioxidant enzymes are associated with diabetic retinopathy in type 1 diabetes

  1. Tinka Hovnik, BSc1,3,
  2. Vita Dolžan, MD2,
  3. Bratina Nataša Uršič, MD1,
  4. Katarina Trebušak Podkrajšek, PHD3 and
  5. Tadej Battelino, MD (tadej.battelino{at},4
  1. 1Department of Pediatric Endocrinology, Diabetes and Metabolic Diseases, University Children's Hospital, UMC, Ljubljana, Slovenia
  2. 2Medical Faculty, Institute of Biochemistry, University of Ljubljana, Ljubljana, Slovenia
  3. 3Center for Medical Genetics, University Children's Hospital, UMC, Ljubljana, Slovenia
  4. 4Medical Faculty, University of Ljubljana, Ljubljana, Slovenia


    Objective: Oxidative stress plays an important role in the development of microangiopathic complications in type 1 diabetes. We investigated polymorphic markers in genes encoding enzymes regulating production of reactive oxygen species in association with diabetic retinopathy (DR) or diabetic nephropathy (DN).

    Research design and methods: One hundred and twenty four 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 MnSOD gene and c.C(-262)T in the promotor region of CAT gene. Multiplex PCR method was used for 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 iNOS.

    Results: A positive association of MnSOD genotype Val/Val (OR = 2.49, 95% CI = 1.00-6.16, P = 0.045) and GSTM1-1 genotype (OR = 2.63, 95% CI = 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 (OR = 4.24, 95% CI = 1.37-13.40, P = 0.009). No other investigated genetic polymorphisms were associated with either DR or DN.

    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 DR.


      • Received May 8, 2009.
      • Accepted September 7, 2009.

    This Article

    1. Diabetes Care
    1. All Versions of this Article:
      1. dc09-0852v1
      2. 32/12/2258 most recent