Heritability of Proliferative Diabetic Retinopathy

Abstract

on behalf of the FinnDiane Study Group 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-TheFinnDiane 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 Ϯ 10.2 years, and mean duration was 25.9 Ϯ 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 ϭ 0.01) of proliferative retinopathy in the siblings of probands (61 of 182). The heritability of proliferative retinopathy was h 2 ϭ 0.52 Ϯ 0.31 (P Ͻ 0.05). After 20 years of diabetes, almost all patients with type 1 diabetes and 58% of patients with type 2 diabetes show signs of retinopathy. When retinopathy worsens, severe visual loss eventually threatens 5-10% of patients (2). The most severe form of retinopathy is proliferative retinopathy, and most of the patients with this complication will become blind after 5-10 years without treatment (3). The prevalence of proliferative retinopathy varies between 13 and 50% after 15-20 years of diabetes duration in patients needing insulin (2,4). CONCLUSIONS-WeThe prevalence of any retinopathy is strongly related to duration and glucose exposure (2,4). Furthermore, poor glycemic control increases the incidence and progression of retinopathy (5,6). Nevertheless, glycemic exposure seems to explain only a part of the risk of proliferative retinopathy (7). In patients with type 2 diabetes, high blood pressure increases the incidence of retinopathy (8). It is noteworthy that proliferative retinopathy is associated with diabetic nephropathy, a complication that is at least in part genetically determined (2). Such an association suggests that familial factors may also contribute to the development of proliferative retinopathy.Therefore, the aim of this study was to elucidate whether there is a familial clustering of proliferative retinopathy in patients with longstanding type 1 diabetes and to estimate the degree of familiality by calculating the heritability of proliferative retinopathy. RESEARCH DESIGN AND METHODSThe present study was undertaken as part of the ongoing FinnDiane Study (Finnish Diabetic Nephropathy Study), a nationwide multicenter project with the aim of identifying genetic and environmenta...

Is There a Relationship between Mean Blood Glucose and Glycated Hemoglobin?

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“…Recently, single nucleotide polymorphisms (SNPs) of several genes were proven to be associated with the progression and severity of DR (Roy et al, 2009). The moderate heritability of proliferative diabetic retinopathy risk (Hietala et al, 2008) suggests the influence of genes on the development of DR.…”

Novel Genetic Actors of Diabetes-Associated Microvascular Complications: Retinopathy, Kidney Disease and Neuropathy

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“…The degree of familial aggregation is greater for more severe forms of retinopathy. Heritability has been estimated to be as high as 27% for DR and 52% for proliferative diabetic retinopathy (PDR), a more advanced form of the disease [13,14].…”