8-Hydroxy-2′-deoxyguanosine is a prognostic mediator for cardiac event
8-Hydroxy-2′-deoxyguanosine is a prognostic mediator for cardiac event
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DOI：
10.1111/j.1365-2362.2010.02465.x
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发表时间：
2011-07-01
影响因子：
5.5
通讯作者：
Kubota, Isao
中科院分区：
文献类型：
--
作者：
Suzuki, Satoshi;Shishido, Tetsuro;Kubota, Isao
研究背景细胞核内的DNA是活性氧的主要靶点之一，DNA氧化损伤与慢性心力衰竭的发病机制有关。8-羟基-2 '-脱氧鸟苷（8-OHdG）是由ROS从DNA中的脱氧鸟苷产生的。方法采用双抗体夹心酶联免疫吸附法（ELISA）检测230例慢性心力衰竭患者和42例非心力衰竭对照者血清8-OHdG水平。结果心力衰竭患者血清8-OHdG浓度高于对照组（P < 0.001），并随纽约心脏协会（NYHA）心功能分级的提高而升高（P <0.001）。8-OHdG水平的正常上限确定为42名对照受试者的平均值+/- 2SD值（0.40 ng mL（-1））。在NYHA I ~ IV级分别有21.2%、43.1%、42.6%和69.4%的患者血清8-OHdG水平异常升高（> 0.40 ng/mL）（P < 0.001）。随访期间共发生66例心脏事件，Kaplan-Meier生存曲线显示，8-OHdG水平高的患者的心脏事件发生率明显高于8-OHdG水平正常的患者（62.4% vs. 29.6%，结论血清8-OHdG水平可作为心力衰竭患者危险分层的重要预后指标。
Background DNA in the nucleus is one of the major targets of reactive oxygen species (ROS), and oxidative DNA damage has been implicated in the pathogenesis of chronic heart failure. 8-Hydroxy-2'-deoxyguanosine (8-OHdG) is produced from deoxyguanosine in DNA by ROS. The purpose of this present study was to examine the clinical significance of serum 8-OHdG levels in patients with heart failure.Methods We measured serum 8-OHdG levels in 230 patients with chronic heart failure and 42 control subjects without heart failure by sandwich enzyme-linked immunosorbent assay. Patients were prospectively followed during a median follow-up period of 472 days with the end points of cardiac death or progressive heart failure requiring re-hospitalization.Results Serum 8-OHdG concentrations were higher in patients with heart failure than in control subjects (P < 0.001) and increased with advancing New York Heart Association (NYHA) functional class (P < 0.001). Normal upper limit of 8-OHdG level was determined as mean +/- 2SD value from 42 control subjects (0.40 ng mL(-1)). Abnormally high serum 8-OHdG levels (> 0.40 ng mL(-1)) were observed in 21.2%, 43.1%, 42.6% and 69.4% through NYHA I to IV (P < 0.001). A total of 66 cardiac events occurred during a follow-up period, and Kaplan-Meier survival curves demonstrated that cardiac event rate was markedly higher in patients with high 8-OHdG levels than in those with normal 8-OHdG levels (62.4% vs. 29.6%, P = 0.0007).Conclusions Serum 8-OHdG levels provide important prognostic information for the risk stratification of patients with heart failure.