Macrophage inhibitory cytokine‐1 (MIC‐1/GDF15): a new marker of all‐cause mortality

• Published in: Aging cell Vol. 9; no. 6; pp. 1057 - 1064
• Main Authors: Wiklund, Fredrik E., Bennet, Anna M., Magnusson, Patrik K. E., Eriksson, Ulrika K., Lindmark, Fredrik, Wu, Liyun, Yaghoutyfam, Nasreen, Marquis, Christopher P., Stattin, Pär, Pedersen, Nancy L., Adami, Hans‐Olov, Grönberg, Henrik, Breit, Samuel N., Brown, David A.
• Format: Journal Article
• Language: English
• Published: Oxford, UK Blackwell Publishing Ltd 01.12.2010
• Subjects: Aged; Aged, 80 and over; Aging; all-cause mortality; Biomarkers - blood; C-Reactive Protein - metabolism; Cardiovascular Diseases - etiology; Cardiovascular Diseases - mortality; Cohort Studies; cytokine; environmental toxicity; Female; Growth Differentiation Factor 15 - blood; Growth Differentiation Factor 15 - genetics; Humans; Interleukin-6 - blood; Kidney Failure, Chronic - etiology; Kidney Failure, Chronic - mortality; Male; MIC-1/GDF15; Middle Aged; Mortality; Neoplasms - etiology; Neoplasms - mortality; prospective observational cohort; Registries; serum marker; Sweden; Sweden
• ISSN: 1474-9718; 1474-9726; 1474-9726
• DOI: 10.1111/j.1474-9726.2010.00629.x

Summary 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.