Serum GDF15 Levels Correlate to Mitochondrial Disease Severity and Myocardial Strain, but Not to Disease Progression in Adult m.3243A>G Carriers
In this observational cohort study, we examined the prognostic value of growth and differentiation factor 15 (GDF15) in indicating and monitoring general mitochondrial disease severity and progression in adult carriers of the m.3243A>G mutation.
Ninety-seven adult carriers of the m.3243A>G mutation were included in this study. The Newcastle mitochondrial disease adult scale was used for rating mitochondrial disease severity. In parallel, blood was drawn for GDF15 analysis by ELISA. Forty-nine carriers were included in a follow-up study. In a small subset of subjects of whom an echocardiogram was available from general patient care, myocardial deformation was assessed using two-dimensional speckle-tracking strain analysis.
A moderate positive correlation was found between the concentration of GDF15 and disease severity (r = 0.59; p < 0.001). The concentration of serum GDF15 was higher in m.3243A>G carriers with diabetes mellitus, cardiomyopathy, and renal abnormalities. After a 2-year follow-up, no significant correlation was found between the change in disease severity and the change in the concentration of GDF15 or between the GDF15 level at the first assessment and the change in disease severity. In the subcohort of patients of whom an echocardiogram was available, the concentration of GDF15 correlated moderately to longitudinal global strain (r = 0.55; p = 0.006; n = 23) but not to circumferential or radial strain.
Our results indicate that serum GDF15 is not a strong surrogate marker for general mitochondrial disease severity. Its value in indicating myocardial deformation should be confirmed in a prospective longitudinal study.
KeywordsMitochondrial Disease Global Longitudinal Strain Myocardial Strain Candidate Predictor Clinical Disease Severity
This work was partly supported by the Netherlands Organisation for Scientific Research (the NWO Centres for Systems Biology Research initiative), ZonMW (AGIKO grants Saskia Koene and Dennis Vriens), and Stichting Energy4All. We thank Inge Konijnenberg-Kramer for sample handling. Jan Smeitink is the CEO of Khondrion BV.
- Association WM (2013) Declaration of Helsinki – ethical principles for medical research involving human subjects. 64th WMA General Assembly, Fortaleza, BrazilGoogle Scholar
- Dominguez-Rodriguez A, Abreu-Gonzalez P, Avanzas P (2014) Usefulness of growth differentiation factor-15 levels to predict diabetic cardiomyopathy in asymptomatic patients with type 2 diabetes mellitus. Am J Cardiol 2:01367–01368Google Scholar
- Kalko SG, Paco S, Jou C et al (2014) Transcriptomic profiling of TK2 deficient human skeletal muscle suggests a role for the p53 signalling pathway and identifies growth and differentiation factor-15 as a potential novel biomarker for mitochondrial myopathies. BMC Genomics 15:91PubMedCentralCrossRefPubMedGoogle Scholar
- Lok SI, Winkens B, Goldschmeding R et al (2012) Circulating growth differentiation factor-15 correlates with myocardial fibrosis in patients with non-ischaemic dilated cardiomyopathy and decreases rapidly after left ventricular assist device support. Eur J Heart Fail 14:1249–1256CrossRefPubMedGoogle Scholar
- Plana JC, Galderisi M, Barac A et al (2014) Expert consensus for multimodality imaging evaluation of adult patients during and after cancer therapy: a report from the American Society of Echocardiography and the European Association of Cardiovascular Imaging. Eur Heart J Cardiovasc Imaging 15:1063–1093CrossRefPubMedGoogle Scholar
- Yang CZ, Ma J, Zhu DW et al (2014) GDF15 is a potential predictive biomarker for TPF induction chemotherapy and promotes tumorigenesis and progression in oral squamous cell carcinoma. Ann Oncol 24:24Google Scholar
- Yatsuga S, Koga Y (2014) Growth differentiation factor 15 and fibroblast growth factor 21: novel biomarkers for mitochondrial diseases United Mitochondrial Disease Foundation Conference 2014Google Scholar