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Growth differentiation factor 15 as a useful biomarker for mitochondrial disorders
Open accessAbstract
OBJECTIVE: The diagnosis of mitochondrial disorders (MDs) is occasionally difficult because patients often present with solitary, or a combination of, symptoms caused by each organ insufficiency, which may be the result of respiratory chain enzyme deficiency. Growth differentiation factor 15 (GDF-15) has been reported to be elevated in serum of patients with MDs. In this study, we investigated whether GDF-15 is a more useful biomarker for MDs than several conventional biomarkers. METHODS: We measured the serum levels of GDF-15 and fibroblast growth factor 21 (FGF-21), as well as other biomarkers, in 48 MD patients and in 146 healthy controls in Japan. GDF-15 and FGF-21 concentrations were measured by enzyme-linked immunosorbant assay and compared with lactate, pyruvate, creatine kinase, and the lactate-to-pyruvate ratio. We calculated sensitivity and specificity and also evaluated the correlation based on two rating scales, including the Newcastle Mitochondrial Disease Rating Scale (NMDAS). RESULTS: Mean GDF-15 concentration was 6-fold higher in MD patients compared to healthy controls (2,711 ± 2,459 pg/ml vs 462.5 ± 141.0 pg/mL; p < 0.001). Using a receiver operating characteristic curve, the area under the curve was significantly higher for GDF-15 than FGF-21 and other conventional biomarkers. Our date suggest that GDF-15 is the most useful biomarker for MDs of the biomarkers examined, and it is associated with MD severity. INTERPRETATION: Our results suggest that measurement of GDF-15 is the most useful first-line test to indicate the patients who have the mitochondrial respiratory chain deficiency.
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“It is considered as an indicator of mitochondrial dysfunction in muscle (21)”
From Human Aging and Longevity Are Characterized by High Levels of Mitokines (2019) · cites this paper as [21]
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Metadata
- Authors
- Yatsuga, S., Fujita, Y., Ishii, A., Fukumoto, Y., Arahata, H., Kakuma, T., Kojima, T., Ito, M., Tanaka, M., Saiki, R., & Koga, Y.
- Affiliations
- Kurume University (JP)
- Tokyo Metropolitan Institute of Gerontology (JP)
- University of Tsukuba (JP)
- Omuta hospital (JP)
- Toyohashi University of Technology (JP)
- Corresponding author
- Koga, Yasutoshi
- ORCID
- Venue
- Annals of Neurology
- Publisher
- Wiley
- Published
- 2015-10-14
- Volume
- 78
- Issue
- 5
- Pages
- 814-823
- ISSN
- 0364-5134 (ISSN-L)
- 1531-8249
- PMC
- PMC5057301
- OpenAlex
- W1903699046
- Cited by
- 293
- References
- 25
- Citations by year
- 2026: 26 · 2025: 29 · 2024: 29 · 2023: 24 · 2022: 32 · 2021: 35 · 2020: 41 · 2019: 31 · 2018: 14 · 2017: 18 · 2016: 13
- FWCI
- 12.59
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Annals of Neurology (publishedVersion, cc-by-nc)
- PubMed Central (publishedVersion, cc-by-nc)
- PubMed (publishedVersion)
- Institutional Repositories DataBase (IRDB) (publishedVersion)
- Terrestrial Environment Research Center (University of Tsukuba) (submittedVersion)
- Funders
- Ministry of Education, Culture, Sports, Science and Technology (MEXT) (25461571 (to Y.K.), 25860891 (to S.Y.), 25242062 (to M.T.))
- The Ministry of Health, Labor and Welfare of Japan. (24-Nanchi-Ippan-005 (to Y.K.) for Research on Intractable Diseases)
- Topics
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › GDF15 and Related Biomarkers
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Mitochondrial Function and Pathology
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Clinical Biochemistry › Metabolism and Genetic Disorders
- Keywords
- growth differentiation factor 15, mitochondrial disease, biomarkers, FGF21, respiratory chain deficiency, serum biomarkers, disease severity, sensitivity and specificity
- MeSH terms
- Adolescent, Adult, Child, Creatine Kinase, Female, Fibroblast Growth Factors, Humans, Male, Middle Aged, ROC Curve, Biomarkers, MELAS Syndrome, Pyruvic Acid, Lactic Acid, Mitochondrial Diseases, Growth Differentiation Factor 15, Young Adult
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