Global DNA methylation as a possible biomarker for diabetic retinopathy
Global DNA methylation as a possible biomarker for diabetic retinopathy
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DOI：
10.1002/dmrr.2584
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发表时间：
2015-02-01
影响因子：
8
通讯作者：
Keshtkar, Abbasali
中科院分区：
文献类型：
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作者：
Maghbooli, Zhila;Hossein-nezhad, Arash;Keshtkar, Abbasali
在一项对168例2型糖尿病患者进行的病例对照研究中，我们评估了全球DNA甲基化水平是否与视网膜病变有关，并提供了DNA甲基化对视网膜病变发展的预测作用。方法采用反相高效液相色谱法测定两组患者外周血白细胞中5-甲基胞嘧啶的含量，以确定两组患者的全球DNA甲基化状态。结果糖尿病视网膜病变患者的全球DNA甲基化水平显著高于非视网膜病变患者(分别为4.900.12vs.4.22+/0.13；P=0.001)。在进展性视网膜病变方面，全球DNA甲基化水平有显著增加的趋势(无视网膜病变，4.22+/-0.13；非增殖性糖尿病视网膜病变，4.62+/-0.17；增殖性糖尿病视网膜病变，5.07+/-0.21)(p=0.006)。此外，全球DNA甲基化独立于视网膜病变危险因素，包括血脂异常、高血压、高血糖和糖尿病病程，是视网膜病变的预测因素(OR=1.53，p=0.015)。这一观察证实了在导致2型糖尿病及其相关并发症的病因过程的早期阶段，高血糖对代谢记忆的影响。版权所有(C)2014 John Wiley&Sons，Ltd.
BackgroundWe 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.MethodsThe 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.ResultsThe global DNA methylation levels were significantly higher in diabetic retinopathy patients compared with those in non-retinopathy patients (4.900.12 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).ConclusionsGlobal 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 (c) 2014 John Wiley & Sons, Ltd.