title: Macrophage inhibitory cytokine-1 (MIC-1/GDF15): a new marker of all-cause mortality.
abstract: 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.
authors.affiliation: Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.
authors.forename: Fredrik E
authors.initials: FE
authors.lastname: Wiklund
authors.forename: Anna M
authors.initials: AM
authors.lastname: Bennet
authors.forename: Patrik K E
authors.initials: PK
authors.lastname: Magnusson
authors.forename: Ulrika K
authors.initials: UK
authors.lastname: Eriksson
authors.forename: Fredrik
authors.initials: F
authors.lastname: Lindmark
authors.forename: Liyun
authors.initials: L
authors.lastname: Wu
authors.forename: Nasreen
authors.initials: N
authors.lastname: Yaghoutyfam
authors.forename: Christopher P
authors.initials: CP
authors.lastname: Marquis
authors.forename: Pär
authors.initials: P
authors.lastname: Stattin
authors.forename: Nancy L
authors.initials: NL
authors.lastname: Pedersen
authors.forename: Hans-Olov
authors.initials: HO
authors.lastname: Adami
authors.forename: Henrik
authors.initials: H
authors.lastname: Grönberg
authors.forename: Samuel N
authors.initials: SN
authors.lastname: Breit
authors.forename: David A
authors.initials: DA
authors.lastname: Brown
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D015415:Biomarkers / Q000097:blood; D002097:C-Reactive Protein / Q000378:metabolism; D002318:Cardiovascular Diseases / Q000209:etiology / Q000401:mortality; D015331:Cohort Studies; D005260:Female; D055436:Growth Differentiation Factor 15 / Q000097:blood* / Q000235:genetics; D006801:Humans; D015850:Interleukin-6 / Q000097:blood; D007676:Kidney Failure, Chronic / Q000209:etiology / Q000401:mortality; D008297:Male; D008875:Middle Aged; D009026:Mortality; D009369:Neoplasms / Q000209:etiology / Q000401:mortality; D012042:Registries; D013548:Sweden
chemical_list: D015415:Biomarkers; C526140:GDF15 protein, human; D055436:Growth Differentiation Factor 15; D015850:Interleukin-6; D002097:C-Reactive Protein