title: 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.
authors: Endocrinology and Metabolism Clinical Sciences Institute, Tehran University of Medical Sciences, Tehran, Iran.
authors: Zhila
authors: Z
authors: Maghbooli
authors: Arash
authors: A
authors: Hossein-nezhad
authors: Bagher
authors: B
authors: Larijani
authors: Manochehr
authors: M
authors: Amini
authors: Abbasali
authors: A
authors: Keshtkar
mesh_terms: D044503:5-Methylcytosine / Q000097:blood / Q000378:metabolism*; D053000:Analytic Sample Preparation Methods; D015415:Biomarkers / Q000097:blood / Q000378:metabolism; D016022:Case-Control Studies; D002851:Chromatography, High Pressure Liquid; D019175:DNA Methylation; D003924:Diabetes Mellitus, Type 2 / Q000150:complications*; D003930:Diabetic Retinopathy / Q000175:diagnosis / Q000453:epidemiology / Q000378:metabolism* / Q000503:physiopathology; D018450:Disease Progression; D005260:Female; D006801:Humans; D006868:Hydrolysis; D007492:Iran / Q000453:epidemiology; D007962:Leukocytes / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D011237:Predictive Value of Tests; D012307:Risk Factors; D015854:Up-Regulation; D018630:Vitreoretinopathy, Proliferative / Q000150:complications / Q000175:diagnosis / Q000453:epidemiology / Q000378:metabolism
chemical_list: D015415:Biomarkers; D044503:5-Methylcytosine
keywords: DNA methylation; diabetic retinopathy; epigenetic; metabolic memory; type 2 diabetes