Global DNA methylation as a possible biomarker for diabetic retinopathy

Abstract

Background: We evaluated whether global levels of DNA methylation status were associated with retinopathy as well as providing a predictive role of DNA methylation in developing retinopathy in a case-control study of 168 patients with type 2 diabetes. Methods: The 5-methylcytosine content was assessed by reversed-phase high-pressure liquid chromatography of peripheral blood leukocytes to determine an individual's global DNA methylation status in the two groups, either with or without retinopathy. Results: The global DNA methylation levels were significantly higher in diabetic retinopathy patients compared with those in non-retinopathy patients (4.90±0.12 vs. 4.22±0.13, respectively; p=0.001). There was a significant increasing trend in global DNA methylation levels in terms of progressing retinopathy (without retinopathy, 4.22±0.13; non-proliferative diabetic retinopathy, 4.62±0.17; proliferative diabetic retinopathy, 5.07±0.21) (p=0.006). Additionally, global DNA methylation independent of retinopathy risk factors, which include dyslipidaemia, hypertension, hyperglycaemia and duration of diabetes, was a predictive factor for retinopathy (OR=1.53, p=0.015). Conclusions: Global DNA methylation is modulated during or possibly before the primary stage of diabetes. This observation verifies the metabolic memory effect of hyperglycaemia in early stage of an aetiological process that leads to type 2 diabetes and its associated complications. Copyright