Heritability of proliferative diabetic retinopathy

Abstract

Objective: Diabetic nephropathy clusters in families suggesting that genetic factors play a role in its pathogenesis. We investigated whether similar clustering exists for proliferative retinopathy in families with two or more siblings with type 1 diabetes.

Research design and methods: The FinnDiane Study has characterized 20% (4800 patients) of adults with type 1 diabetes in Finland. In 188 families there were at least two siblings with type 1 diabetes. Ophthalmic records were obtained for 369/396 (93%) and fundus photographs for 251/369 (68%) patients. Retinopathy was graded based on photographs and/or repeated ophthalmic examinations using the ETDRS-grading scale.

Results: Mean age at onset of diabetes was 14.3 (±10.2) years and mean duration 25.9 (±11.8) years. Proliferative retinopathy was found in 115/369 patients (31%). The familial risk of proliferative retinopathy was estimated in 168/188 sibships, adjusted for HbA_1c, duration and mean blood pressure. Proliferative retinopathy in the probands (48/168) was associated with an increased risk (Odds Ratio [OR] 2.76 [95% CI 1.25- 6.11], P=0.01) of proliferative retinopathy in the siblings of probands (61/182). The heritability of proliferative retinopathy was h2=0.52 (± 0.31, P<0.05).

Conclusions: We found a familial clustering of proliferative retinopathy in patients with type 1 diabetes. The observation cannot be accounted for by conventional risk factors, suggesting a genetic component in the pathogenesis of proliferative retinopathy in type 1 diabetes.