Diabetes duration may modify the association between genetic variation in the glycoprotein la subunit of the platelet collagen receptor and risk of severe diabetic retinopathy: a working hypothesis

Genetic factors appear to contribute to the severity and progression of diabetic retinopathy. We assessed the associations of the C807T and Glu505Lys variants of the glycoprotein Ia (alpha(2) integrin) subunit of the platelet/endothelial collagen receptor and risk of retinopathy in a population-based survey of 288 diabetic patients in one Swedish community. Neither variant was associated with retinopathy risk overall. However, the 807T variant was associated with increased risk of severe retinopathy, and the association was modified by diabetes duration. Among patients with diabetes of longer duration (greater than or equal to25 years), the 807T variant was strongly associated with risk of severe retinopathy (odds ratio 7.49, 95% confidence interval 1.75 to 32.1). There was no association between the 807T variant and risk of severe retinopathy among patients with diabetes duration <25 years. The Lys505 variant of glycoprotein la was associated with an odds ratio for severe retinopathy of 1.88 (95% confidence interval 0.83, to 4.24). Overall, there was a significant interaction between glycoprotein la genotype and duration of diabetes on the risk of retinopathy (P-value for interaction = 0.019). These results suggest the hypothesis that genetic variation of platelet glycoprotein la may play a particularly important role during the advanced stages of. diabetic retinopathy.