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Résultats du PHRC prospectif multicentrique REDIAGEN : pas d’association entre rétinopathie diabétique proliférante et polymoprhismes de la lipase endothéliale et de l’aldose réductase

To prospectively investigate in patients with type 2 diabetes (T2D) the association between the development of proliferative diabetic retinopathy (PDR) and polymorphisms in endothelial lipase (EL c.584C>T) and aldose reductase (AR C(-106)T), which have previously been identified in retrospective studies as being associated with PRD.

Prospective multicenter case-control study comparing 146 French patients with T2D with PDR (cases) and 146 French patients with T2D without PDR (controls) on the basis of two genetic polymorphisms: EL c.584C>T and AR C(-106)T. Participation in the study was offered to any T2D patient managed for PDR in one of the 5 participating centers (X1, X2, X3, X4, X5) and for each included case, to a patient with T2D without PDR, so that cases and controls were matched on sex, age, and duration of T2D evolution. After acceptance, clinical and biological data were collected and a blood sample for genetic analysis was taken. Comparison of cases and controls by univariate analysis (Student's, Wilcoxon, Chi2 or Fisher's exact tests) and then multivariate analysis (logistic regression) was performed with SAS software to look for risk factors. P<0.05 was considered statistically significant.

For endothelial lipase c584C>T polymorphisms, these appeared to be similarly distributed between cases (CC 55%, TC 38%, TT 7%) and controls (CC 51%, TC 43%, TT 6%). The same was true for aldose reductase C(-106)T polymorphisms between cases (GG 43%, AG 43%, AA 14%) and controls (GG 38%, AG 46%, AA 16%). After matching on age, sex and duration of diabetes, no statistically significant difference was found between the 2 groups of cases and controls regarding the distributions of these two polymorphisms in univariate analysis (p=0.45). In multivariate analysis, after adjustment for different parameters statistically associated with cases of proliferative diabetic retinopathy (presence of rubeosis iridis OR=7.5, p=0.0074, diabetic macular oedema OR=8.0 p<0.001, tractional retinal detachment OR=9.0 p=0.037, history of retinal photocoagulation OR=34.0 p<0.001, patient's height OR=20.7 p=0.028), the results for the polymorphisms investigated remained similar in the two study groups (p=0.32).

The results of this prospective multicentre study make it possible to rule out the role of these two polymorphisms in proliferative forms of diabetic retinopathy. The constitution of this large REDIAGEN cohort composed of well-phenotyped patients with associated plasma and DNA banks should make it possible to continue association studies in order to find new protective or poor prognostic genetic markers of evolution towards a proliferating form. 

We found no association of endothelial lipase and aldose reductase polymorphisms with proliferative diabetic retinopathy