Association between a protein polymorphism in the start codon of the vitamin D receptor gene and severe diabetic retinopathy in C-peptide-negative type 1 diabetes

J Clin Endocrinol Metab. 2005 Aug;90(8):4803-8. doi: 10.1210/jc.2004-2407. Epub 2005 May 17.


Context: The vitamin D (VD) receptor (VDR) is extensively expressed in retina. The plasma concentration of 1,25-dihydroxyvitamin D3 has been inversely correlated with the severity of diabetic retinopathy (DR), which raises the possibility that VD, through its antiinflammatory, antioxidant, antiproliferative, and antiangiogenic properties, may protect diabetic retina. The TaqI VDR polymorphism has been associated with severe DR. The FokI VDR polymorphism is a T-to-C substitution in the first codon (f allele), abolishing the first translation initiation site and resulting in a peptide lacking three amino acids (F allele), which increases the transcriptional activity of VDR.

Objective and design: To examine whether FokI polymorphism is involved in severe DR, 254 Caucasians with longstanding C-peptide-negative type 1 diabetes, 128 patients with absent/mild DR (control group), and 126 patients with preproliferative/proliferative DR (study group) were genotyped using PCR-restriction fragment length polymorphism analysis.

Results: The genotype distribution was in Hardy-Weinberg equilibrium and was different between groups (P = 0.046). The frequency of F allele was significantly higher in the control (66.4%) than in the study group (56%, odds ratio = 0.64, 95% confidence interval 0.44-0.92, P = 0.016). In subjects with fewer than 25 yr of diabetes duration (median value, n = 134), this association was strongly increased (P = 0.0008).

Conclusions: In conclusion, we observed, in a cohort of Caucasians with C-peptide-negative type 1 diabetes, a novel association between the functional FokI VDR polymorphism and severe DR, especially among subjects with fewer than 25 yr of diabetes duration.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • C-Peptide / blood
  • Case-Control Studies
  • Codon, Initiator
  • Diabetes Mellitus, Type 1 / blood
  • Diabetes Mellitus, Type 1 / epidemiology
  • Diabetes Mellitus, Type 1 / genetics*
  • Diabetic Nephropathies / blood
  • Diabetic Nephropathies / epidemiology
  • Diabetic Nephropathies / genetics
  • Diabetic Retinopathy / blood
  • Diabetic Retinopathy / epidemiology
  • Diabetic Retinopathy / genetics*
  • Female
  • Glycated Hemoglobin A / metabolism
  • Humans
  • Male
  • Middle Aged
  • Polymorphism, Genetic*
  • Receptors, Calcitriol / genetics*
  • Risk Factors
  • Severity of Illness Index
  • Whites / genetics


  • C-Peptide
  • Codon, Initiator
  • Glycated Hemoglobin A
  • Receptors, Calcitriol