Impact of inflammation on epigenetic DNA methylation -: a novel risk factor for cardiovascular disease?
Impact of inflammation on epigenetic DNA methylation -: a novel risk factor for cardiovascular disease?
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DOI：
10.1111/j.1365-2796.2007.01777.x
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发表时间：
2007-05-01
影响因子：
11.1
通讯作者：
Schalling, M.
中科院分区：
文献类型：
--
作者：
Stenvinkel, P.;Karimi, M.;Schalling, M.
目的：透析患者的寿命与转移性癌症患者一样短，主要是由于心血管疾病（CVD）。DNA甲基化是一个重要的细胞机制，调节与衰老，炎症和动脉粥样硬化processes.Design相关的基因表达：DNA甲基化进行了分析，在外周血白细胞从三个不同的慢性肾脏病（CKD）人群（37 CKD阶段3和4患者，98 CKD阶段5患者和20流行的血液透析患者）。36名健康受试者作为对照。评价了临床特征（糖尿病、营养状况和临床CVD的存在）、炎症和氧化应激生物标志物、同型半胱氨酸和外周血白细胞中的总体DNA甲基化（通过发光甲基化测定法定义为HpaII/MspI比值）。CKD 5期患者（n = 98）开始透析治疗后，为期36 +/-2 months.Results：炎症患者HpaII/MspI的比率较低，表明全球DNA高甲基化。通过考克斯回归模型分析表明，DNA高甲基化（HpaII/MspI比值<中位数）与全因（RR 5.0; 95% CI：1.7 - 14.8; P <0.01）（RR 13.9; 95%CI：1.8 - 109.3; P <0.05）死亡率，即使调整了年龄、CVD、糖尿病和炎症。目前的研究表明，整体DNA超甲基化与CKD的炎症和死亡率增加有关。
Objective: The lifespan of dialysis patients is as short as in patients with metastatic cancer disease, mainly due to cardiovascular disease (CVD). DNA methylation is an important cellular mechanism modulating gene expression associated with ageing, inflammation and atherosclerotic processes.Design: DNA methylation was analysed in peripheral blood leucocytes from three different groups of chronic kidney disease (CKD) populations (37 CKD stages 3 and 4 patients, 98 CKD stage 5 patients and 20 prevalent haemodialysis patients). Thirty-six healthy subjects served as controls. Clinical characteristics (diabetes mellitus, nutritional status and presence of clinical CVD), inflammation and oxidative stress biomarkers, homocysteine and global DNA methylation in peripheral blood leucocytes (defined as HpaII/MspI ratio by the Luminometric Methylation Assay method) were evaluated. CKD stage 5 patients (n = 98) starting dialysis treatment were followed for a period of 36 +/- 2 months.Results: Inflamed patients had lower ratios of HpaII/MspI, indicating global DNA hypermethylation. Analysis by the Cox regression model demonstrated that DNA hypermethylation (HpaII/MspI ratio < median) was significantly associated with both all-cause (RR 5.0; 95% CI: 1.7-14.8; P < 0.01) and cardiovascular (RR 13.9; 95% CI: 1.8-109.3; P < 0.05) mortality, even following the adjustment for age, CVD, diabetes mellitus and inflammation.Conclusion: The present study demonstrates that global DNA hypermethylation is associated with inflammation and increased mortality in CKD.