Heritability of proliferative diabetic retinopathy.
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.


METHODS
The FinnDiane Study has characterized 20% (4,800 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 of 396 (93%) and fundus photographs for 251 of 369 (68%) patients. Retinopathy was graded based on photographs and/or repeated ophthalmic examinations using the Early Treatment of Diabetic Retinopathy grading scale.


RESULTS
Mean age at onset of diabetes was 14.3 +/- 10.2 years, and mean duration was 25.9 +/- 11.8 years. Proliferative retinopathy was found in 115 of 369 patients (31%). The familial risk of proliferative retinopathy was estimated in 168 of 188 sibships, adjusted for A1C, duration, and mean blood pressure. Proliferative retinopathy in the probands (48 of 168) was associated with an increased risk (odds ratio 2.76 [95% CI 1.25- 6.11], P = 0.01) of proliferative retinopathy in the siblings of probands (61 of 182). The heritability of proliferative retinopathy was h(2) = 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.
Hietala
Kustaa
K
Folkhälsan Institute of Genetics, Folkhälsan Research Center, Biomedicum Helsinki, Helsinki, Finland.
Forsblom
Carol
C
Summanen
Paula
P
Groop
Per-Henrik
PH
D000293:Adolescent; D000328:Adult; D017668:Age of Onset; D002648:Child; D002675:Child, Preschool; D003922:Diabetes Mellitus, Type 1 / Q000453:epidemiology / Q000235:genetics / Q000473:pathology; D003930:Diabetic Retinopathy / Q000453:epidemiology* / Q000235:genetics* / Q000473:pathology; D005192:Family Health; D005260:Female; D005387:Finland / Q000453:epidemiology; D006801:Humans; D008297:Male; D016017:Odds Ratio; D012307:Risk Factors; D035781:Siblings