ACE gene polymorphism and proliferative retinopathy in type 1 diabetes - results of a case-control study

OBJECTIVE - To evaluate the relationship between the ACE insertion/deletion polymorphism and proliferative diabetic retinopathy in patients with type 1 diabetes of long duration. Based on epidemiological and pathophysiologica l findings, risk factors apart from glycemic control and duration of diseas e are likely to be involved in the development of proliferative retinopathy . RESEARCH DESIGN AND METHODS - In this case-control study we compared 81 pat ients with longstanding (greater than or equal to 20 years) type 1 diabetes who had nonproliferative (mild or moderate background) retinopathy with 95 patients with diabetes of similar duration and HbA(1c) who had proliferati ve retinopathy. To avoid the confounding effect of nephropathy, patients wi th overt nephropathy were excluded, and microalbuminuria was introduced int o the multiple logistical regression model,The polymorphic region in intron 16 of the ACE gene (17q23) was analyzed using the polymerase chain reactio n. RESULTS - The ACE genotype distribution in patients with proliferative reti nopathy (DD 39.4%, ID 48.9%, II 11.7%) was significantly different (P < 0.0 01) from that of patients with nonproliferative retinopathy (DD 17.3%, ID 5 4.3%, II 28.4%). In a multiple logistical regression analysis, the adjusted relative risk for proliferative retinopathy in a patient with a DD genotyp e compared with a patient with an II genotype was 6.6 (95% CI 2.2-19.5), P = 0.0026. In addition to genotype, systolic blood pressure (odds ratio 1.02 7 [95% CI 1.0-1.1], P = 0.0093) but not microalbuminuria (less than or equa l to 20 vs. greater than or equal to 20 mu g/min) reached statistical signi ficance in the multi pie regression model. Because subjects were matched re garding diabetes duration and HbA(1c), we did not interpret the respective parameter estimates. CONCLUSIONS - These data provide evidence that deletion in the ACE gene is associated with the prevalence of proliferative retinopathy in type 1 diabe tes and suggest that the DD genotype confers susceptibility to proliferativ e retinopathy independent of diabetic nephropathy.