Hypermethylation in the promoter of the MTHFR gene is associated with diabetic complications and biochemical indicators.

Hypermethylation in the promoter of the MTHFR gene is associated with diabetic complications and biochemical indicators.
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DOI:
10.1186/s13098-017-0284-3
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发表时间:
2017
影响因子:
4.8
通讯作者:
Persuhn DC
Persuhn DC
中科院分区:
医学2区
文献类型:
--
作者:
Dos Santos Nunes MK;Silva AS;de Queiroga Evangelista IW;Filho JM;Gomes CNAP;do Nascimento RAF;Luna RCP;de Carvalho Costa MJ;de Oliveira NFP;Persuhn DC

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DNA甲基化是调节许多基因转录的表观遗传机制,与多种疾病的发生有关。一个有希望研究的基因是亚甲基四氢叶酸还原酶(MTHFR),因为亚甲基四氢叶酸还原酶(MTHFR)促进同型半胱氨酸循环中的甲基自由基合成,并且可以为DNA甲基化提供甲基。此外,一些研究已将这种酶的基因多态性与较高的糖尿病风险相关联,但对该基因的表观遗传变化与糖尿病及其并发症之间的关系知之甚少。本研究的目的是调查 2 型糖尿病 (T2DM) 患者的 MTHFR 基因启动子甲基化谱与生化、炎症和氧化应激标志物之间的关系,这些患者已被诊断患有或不患有糖尿病视网膜病变 (DR) 和肾病 (DN) 5-10 年。甲基化特异性 PCR (MSP) 用于分析白细胞 DNA 中的 MTHFR 甲基化谱。测定外周血样本中的生化标志物(血糖、糖化血红蛋白、总胆固醇、低密度脂蛋白、高密度脂蛋白、甘油三酯、血清肌酐)、炎症标志物(C反应蛋白和α-1酸性糖蛋白)和氧化应激(总抗氧化剂和丙二醛)和微量白蛋白尿。 24 小时尿液样本。进行了 X2 和 Mann-Whitney 统计检验,p < 0.05 被认为是显着的。高甲基化特征最常见于视网膜病变个体(p < 0.01),并且与较高的总胆固醇和 LDL 水平相关(分别为 p = 0.0046、0.0267)。与没有并发症的受试者相比,具有 DN 和高甲基化特征的个体具有更高水平的 α-1 酸性糖蛋白 (p = 0.0080) 和总抗氧化能力 (p = 0.0169)。 MTHFR 基因启动子的高甲基化与 DR 的发生以及慢性并发症中的生化、炎症和氧化应激参数相关
DNA methylation is an epigenetic mechanism for regulating the transcription of many genes and has been linked to the development of various diseases. A promising gene to investigate is methylenetetrahydrofolate reductase (MTHFR), since the enzyme methylenetetrahydrofolate reductase (MTHFR) promotes methyl radical synthesis in the homocysteine cycle and can provide methyl groups for DNA methylation. In addition, several studies have correlated gene polymorphisms of this enzyme with a greater risk of diabetes, but little is known regarding the relationship between epigenetic changes in this gene and diabetes and its complications. The aim of this study was to investigate the relationship between methylation profile in the MTHFR gene promoter and biochemical, inflammatory and oxidative stress markers in individuals with type 2 diabetes (T2DM) who have been diagnosed for 5–10 years with or without diabetic retinopathy (DR) and nephropathy (DN). Specific PCR for methylation (MSP) was used to analyze MTHFR methylation profile in leucocytes DNA. Biochemical markers (glycemia, glycated hemoglobin, total cholesterol, LDL, HDL, triglycerides, serum creatinine), inflammatory markers (C-reactive protein and alpha-1 acid glycoprotein) and oxidative stress (total antioxidant and malonaldehyde) were determined in peripheric blood samples and microalbuminuria in 24 h urine samples. The X2 and Mann–Whitney statistical tests were performed and p < 0.05 were considered significant. The hypermethylated profile was most frequently observed in individuals with retinopathy (p < 0.01) and was associated with higher total cholesterol and LDL levels (p = 0.0046, 0.0267, respectively). Individuals with DN and hypermethylated profiles had higher levels of alpha-1 acid glycoprotein (p = 0.0080) and total antioxidant capacity (p = 0.0169) compared to subjects without complications. Hypermethylation in the promoter of the MTHFR gene is associated with the occurrence of DR and with biochemical, inflammatory and oxidative stress parameters in the context of chronic complications
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