Taq I polymorphism of the vitamin D receptor and risk of severe diabetic retinopathy

Abstract

Neovascularization plays a role in determining the severity of diabetic retinopathy (DR) due to the effects of several angiogenic and growth factors, including vascular endothelial growth factor (VEGF), plateletderived growth factor (PDGF), basic fibroblast growth factor (bFGF) and insulin-like growth factor (IGF-1) [1].Chronic hyperglycaemia induces non-severe diabetic retinopathy (DR) in most patients of long duration, but not severe DR in the majority of them, sug- Abstract Aims/hypothesis. 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 1 c : 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 c 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 c 2 (df = 2): p = 0.024. In subjects with HbA 1 c 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 c 2 (df = 2): p = 0.035. Conclusion/interpretation. In French Type I (insulindependent) 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. [Diabetologia (2002) 45: 436±442]

Vitamin D receptor gene polymorphisms in type 1 diabetes mellitus: a new pattern from Khorasan province, Islamic Republic of Iran

“…Taverna et al in Paris observed 200 patients with type 1 DM and found that the Tt genotype was associated with severe retinopathy. In that study, patients with TT genotype were low risk for severe diabetic retinopathy [26]. We found no association between VDR gene polymorphisms and diabetic retinopathy.…”

Adherence to diabetic eye examination guidelines in Australia: the National Eye Health Survey

“…Other gene polymorphisms in the RAGE gene 325 , the TGF-beta1 gene 326 , the VEGF gene [327][328][329][330] , the eNOS (endothelial nitric oxide synthase) gene 330 and vitamin D receptor 331 have also been associated with the presence or severity of DR from case-control studies. A meta-analysis that examined the association between DR in T2DM and polymorphisms in the gene for hyper-homocystinaemia (methylenetetrahydrofolate reductase, MTHFR) found only a marginal association with large heterogeneity between different studies 332 .…”

Biomarkers in Diabetic Retinopathy

“…Vitamin D receptor-related genotypes have been associated with diabetic retinopathy in type 1 and type 2 diabetic subjects [249][250][251][252][253][254]. Similar to its known role in bone and calcium metabolism, vitamin D also has roles in insulin resistance and immune function, and it has anti-inflammatory, anti-angiogenic, and anti-fibrotic effects.…”