Abstract
Background: Diabetic retinopathy is a long-term complication of type 2 diabetes (T2D). Non-diabetic retinopathy may be present in T2D patients as well and non-T2D patients with hypertension and/or atherosclerosis. The aim of this study was to identify linkage of the proteasome modulator 9 (PSMD9) T2D risk variants IVS3+nt460, IVS3+nt437, E197G to diabetic retinopathy and retinopathy including also atherosclerotic or hypertensive retinopathy in Italian T2D families. Materials and Methods: A total of 126 siblings of our 200 T2D siblings/families were characterized for diabetic retinopathy or retinopathy. The clinical characterization is based on a fundus oculi exam and on fluorangiography of the participating subjects. Diabetic retinopathy includes both pre-proliferative and proliferative retinopathy. The common gene variants were directly amplified by PCR and by fluorescent-based automation. A parametric and non-parametric linkage study of the gene variants with diabetic retinopathy and retinopathy was then performed using Merlin software. Finally, 1000 simulation analyses were performed to test for the statistical power of the significant results (P-value ≤ 0.05). Results: This study shows a linkage of the PSMD9 IVS3+nt460 (rs74421874), IVS3+nt437 (rs3825172) and E197G (rs14259) single nucleotide polymorphisms (SNPs) to diabetic and non-diabetic retinopathy by using the non-parametric as well as the parametric linkage analysis. The strongest signal is present for the PSMD9 variants with the diabetic retinopathy, in particular under the additive model. The 1,000 simulations performed for each significant test confirmed that the results are not due to random chance. Conclusions: In summary, the PSMD9 IVS3+nt460, IVS3+nt437, E197G SNPs are linked to diabetic retinopathy and non-diabetic retinopathy in Italians.