title: Genetic polymorphisms in genes encoding antioxidant enzymes are associated with diabetic retinopathy in type 1 diabetes.
abstract: 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 or diabetic nephropathy.
  
  
  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-262T in the promoter region of the 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 inducible nitric oxide synthase.
  
  
  RESULTS
  A positive association of MnSOD genotype Val/Val (odds ratio [OR] 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 other investigated 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.
authors.affiliation: Department of Pediatric Endocrinology, Diabetes and Metabolic Diseases, University Children's Hospital, University Medical Centre, Ljubljana, Slovenia.
authors.forename: Tinka
authors.initials: T
authors.lastname: Hovnik
authors.forename: Vita
authors.initials: V
authors.lastname: Dolzan
authors.forename: Natasa Ursic
authors.initials: NU
authors.lastname: Bratina
authors.forename: Katarina Trebusak
authors.initials: KT
authors.lastname: Podkrajsek
authors.forename: Tadej
authors.initials: T
authors.lastname: Battelino
mesh_terms: D000328:Adult; D017668:Age of Onset; D019943:Amino Acid Substitution; D016022:Case-Control Studies; D003922:Diabetes Mellitus, Type 1 / Q000201:enzymology / Q000235:genetics*; D003930:Diabetic Retinopathy / Q000201:enzymology / Q000235:genetics*; D005260:Female; D005787:Gene Frequency; D006580:Genetic Carrier Screening; D005819:Genetic Markers; D005982:Glutathione Transferase / Q000235:genetics*; D006442:Glycated Hemoglobin / Q000378:metabolism; D006801:Humans; D008297:Male; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic; D017382:Reactive Oxygen Species / Q000378:metabolism; D012016:Reference Values; D013482:Superoxide Dismutase / Q000235:genetics*; D055815:Young Adult
chemical_list: D005819:Genetic Markers; D005982:Glutathione Transferase; D006442:Glycated Hemoglobin; D017382:Reactive Oxygen Species; D013482:Superoxide Dismutase