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非重度慢性阻塞性肺疾病(COPD)患者的全血 DNA 甲基化水平降低。

Blood global DNA methylation is decreased in non-severe chronic obstructive pulmonary disease (COPD) patients.

机构信息

Department of Biomedical Sciences - University of Sassari, Sassari, Italy.

Department of Clinical and Experimental Medicine, University of Sassari, Sassari, Italy; Department of Respiratory Diseases, University Hospital Sassari (AOU), Sassari, Italy.

出版信息

Pulm Pharmacol Ther. 2017 Oct;46:11-15. doi: 10.1016/j.pupt.2017.08.006. Epub 2017 Aug 14.

Abstract

BACKGROUND

Alterations in global DNA methylation have been associated with oxidative stress (OS). Since chronic obstructive pulmonary disease (COPD) is characterized by increased oxidative stress we aimed to evaluate the levels of global DNA methylation in this patient group.

METHODS

We assessed methylcytosine (mCyt) levels in DNA from blood collected in 43 COPD patients (29 with mild and 14 with moderate disease) and 43 age- and sex-matched healthy controls.

RESULTS

DNA methylation was significantly lower in COPD patients vs. controls (4.20 ± 0.18% mCyt vs. 4.29 ± 0.18% mCyt, p = 0.02). Furthermore, DNA methylation in COPD patients with moderate disease was significantly lower than that in patients with mild disease (4.14 ± 0.15% mCyt vs. 4.23 ± 0.19% mCyt, p < 0.05). Univariate logistic regression analysis showed that lower DNA methylation levels were associated with presence of COPD (crude OR = 0.06, 95% CI 0.00 to 0.67, p = 0.023). This relationship remained significant after adjusting for several confounders (OR 0.03, 95% CI 0.00 to 0.67; p = 0.028). Receiver operating characteristics (ROC) curve analysis demonstrated the area under the curve of mCyt was 0.646, with 46.6% sensitivity and 79.1% specificity for presence of COPD.

CONCLUSIONS

There were no significant correlations between methylation and OS indices. The presence and severity of COPD is associated with progressively lower DNA methylation in blood. However, this epigenetic alteration seems independent of oxidative stress.

摘要

背景

全基因组 DNA 甲基化的改变与氧化应激(OS)有关。由于慢性阻塞性肺疾病(COPD)的特征是氧化应激增加,我们旨在评估该患者群体的全基因组 DNA 甲基化水平。

方法

我们评估了来自 43 名 COPD 患者(29 名轻度和 14 名中度)和 43 名年龄和性别匹配的健康对照者血液中 DNA 的甲基胞嘧啶(mCyt)水平。

结果

与对照组相比,COPD 患者的 DNA 甲基化水平显著降低(4.20±0.18% mCyt 比 4.29±0.18% mCyt,p=0.02)。此外,中度疾病 COPD 患者的 DNA 甲基化水平明显低于轻度疾病患者(4.14±0.15% mCyt 比 4.23±0.19% mCyt,p<0.05)。单因素 logistic 回归分析显示,较低的 DNA 甲基化水平与 COPD 的存在相关(未校正 OR=0.06,95%CI 0.00 至 0.67,p=0.023)。调整了几个混杂因素后,这种关系仍然显著(OR 0.03,95%CI 0.00 至 0.67;p=0.028)。接受者操作特征(ROC)曲线分析表明,mCyt 的曲线下面积为 0.646,对 COPD 的存在具有 46.6%的敏感性和 79.1%的特异性。

结论

甲基化与 OS 指标之间没有显著相关性。COPD 的存在和严重程度与血液中 DNA 甲基化程度的逐渐降低有关。然而,这种表观遗传改变似乎独立于氧化应激。

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