Macrophage inhibitory cytokine-1 (MIC-1/GDF15): a new marker of all-cause mortality
Macrophage inhibitory cytokine-1 (MIC-1/GDF15): a new marker of all-cause mortality
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DOI：
10.1111/j.1474-9726.2010.00629.x
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发表时间：
2010-12-01
期刊：
影响因子：
7.8
通讯作者：
Brown, David A.
中科院分区：
文献类型：
--
作者：
Wiklund, Fredrik E.;Bennet, Anna M.;Brown, David A.
巨噬细胞抑制性细胞因子-1（MIC-1/GDF 15）是TGF-β超家族的成员，以前在癌症和炎症中进行了研究。除了调节体重外，MIC-1/GDF 15还可用于预测癌症、心血管疾病（CVD）、慢性肾衰竭和心力衰竭以及肺栓塞的死亡率和/或病程。这些数据表明MIC-1/GDF 15可能是全因死亡率的标志物。为了确定血清MIC-1/GDF 15估计值是否是全因死亡率的预测因子，我们检查了从瑞典人口登记处选择的876名年龄在35-80岁的男性受试者的队列，并随访了他们的总体死亡率。从进入研究时采集的样品测定所有受试者的血清MIC-1/GDF 15水平。第二个（独立）队列的324同性双胞胎（69%女性）从瑞典双胞胎登记处进行了类似的检查。所有的双胞胎都测量了端粒长度，183例有血清白细胞介素6（IL-6）和C反应蛋白（CRP）水平。患者随访长达14年，并确定了病因特异性和全因死亡率。血清MIC-1/GDF 15水平预测全男性队列的死亡率，校正后的死亡比值比（OR）为3.38（95%CI 1.38-8.26）。这一发现在双胞胎队列中得到了验证。当进一步校正端粒长度、IL-6和CRP时，血清MIC-1/GDF 15仍然是死亡率的独立预测因子。此外，血清MIC-1/GDF 15水平与生存时间直接相关，与遗传背景无关。血清MIC-1/GDF 15是全因死亡率的新预测因子。
P>Macrophage inhibitory cytokine-1 (MIC-1/GDF15) is a member of the TGF-b superfamily, previously studied in cancer and inflammation. In addition to regulating body weight, MIC-1/GDF15 may be used to predict mortality and/or disease course in cancer, cardiovascular disease (CVD), chronic renal and heart failure, as well as pulmonary embolism. These data suggested that MIC-1/GDF15 may be a marker of all-cause mortality. To determine whether serum MIC-1/GDF15 estimation is a predictor of all-cause mortality, we examined a cohort of 876 male subjects aged 35-80 years, selected from the Swedish Population Registry, and followed them for overall mortality. Serum MIC-1/GDF15 levels were determined for all subjects from samples taken at study entry. A second (independent) cohort of 324 same-sex twins (69% female) from the Swedish Twin Registry was similarly examined. All the twins had telomere length measured and 183 had serum levels of interleukin 6 (IL-6) and C-reactive protein (CRP) available. Patients were followed for up to 14 years and had cause-specific and all-cause mortality determined. Serum MIC-1/GDF15 levels predicted mortality in the all-male cohort with an adjusted odds ratio (OR) of death of 3.38 (95%CI 1.38-8.26). This finding was validated in the twin cohort. Serum MIC-1/GDF15 remained an independent predictor of mortality when further adjusted for telomere length, IL-6 and CRP. Additionally, serum MIC-1/GDF15 levels were directly correlated with survival time independently of genetic background. Serum MIC-1/GDF15 is a novel predictor of all-cause mortality.