title: Taq I polymorphism of the vitamin D receptor and risk of severe diabetic retinopathy.
abstract: OBJECTIVE
  Vitamin D, a molecule with antiproliferative, antiangiogenic, antioxidant and immunosuppressive effects, could play a role in the pathogenesis of severe diabetic retinopathy. We examined whether Taq I polymorphism of the vitamin D receptor is involved in the development of severe diabetic retinopathy.
  
  
  METHODS
  200 unrelated C-peptide-negative French Type I diabetic patients were randomly selected (male:female, 103:97, age 44.4 +/- 12.4 years, diabetes duration: 27.7 +/- 10.0 years, BMI: 24.3 +/- 3.4 kg/m(2), HbA(1c): 8.6 +/- 1.3 %). The Taq I site was analysed by PCR followed by digestion with Taq I enzyme. Diabetic retinopathy was assessed by retinal angiography and classified as presence (n = 101) or absence (n = 99) of severe (preproliferative or proliferative) diabetic retinopathy.
  
  
  RESULTS
  Frequency of wild-type genotype TT was lower in patients with severe diabetic retinopathy (n = 27) when compared with control subjects (n = 42, OR = 0.5, p = 0.028). Allele frequencies were not different between patients (T: n = 112 and t: n = 90) and control subjects (T: n = 128, and t: n = 70, p = 0.075). Global chi(2) (df = 2): p = 0.064. In subjects with diabetes duration of more than 25 years, TT was lower in severe diabetic retinopathy (n = 14) than control subjects (n = 18, OR = 0.3, p = 0.01). Allele frequencies were different between patients (T: n = 68 and t: n = 66) and control subjects (T: n = 52, OR = 0.5, and t: n = 26, OR = 1.9, p = 0.034). Global chi(2) (df = 2): p = 0.024. In subjects with HbA(1c) over 9 %, Tt was higher in patients (n = 28) than control subjects (n = 15, OR = 3.1, p = 0.019). Allele frequencies were not different between patients (T: n = 52 and t: n = 38) and control subjects (T: n = 57, and t: n = 29, p = 0.31). Global chi(2) (df = 2): p = 0.035.
  
  
  CONCLUSIONS
  In French Type I (insulin-dependent) diabetic patients, we demonstrate an association between TT form (VDR) and low risk for severe diabetic retinopathy, especially in patients with long duration, and between Tt variant and high risk for severe diabetic retinopathy in subjects with poor glycaemic control.
authors.affiliation: INSERM U341, Hôtel-Dieu Hospital, Paris, France.
authors.forename: M J
authors.initials: MJ
authors.lastname: Taverna
authors.forename: A
authors.initials: A
authors.lastname: Sola
authors.forename: C
authors.initials: C
authors.lastname: Guyot-Argenton
authors.forename: N
authors.initials: N
authors.lastname: Pacher
authors.forename: F
authors.initials: F
authors.lastname: Bruzzo
authors.forename: G
authors.initials: G
authors.lastname: Slama
authors.forename: G
authors.initials: G
authors.lastname: Reach
authors.forename: J-L
authors.initials: JL
authors.lastname: Selam
mesh_terms: D000328:Adult; D017668:Age of Onset; D002096:C-Peptide / Q000097:blood; D004247:DNA / Q000097:blood / Q000235:genetics; D015252:Deoxyribonucleases, Type II Site-Specific / Q000235:genetics*; D003922:Diabetes Mellitus, Type 1 / Q000097:blood / Q000235:genetics*; D003930:Diabetic Retinopathy / Q000453:epidemiology*; D005260:Female; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic; D018167:Receptors, Calcitriol / Q000235:genetics*; D012016:Reference Values; D015183:Restriction Mapping; D012307:Risk Factors
chemical_list: D002096:C-Peptide; D018167:Receptors, Calcitriol; D004247:DNA; D015252:Deoxyribonucleases, Type II Site-Specific; C027046:TCGA-specific type II deoxyribonucleases