Growth and differentiation factor 15 as a biomarker for mitochondrial myopathy

Poulsen, Nanna Scharff; Madsen, Karen L.; Hornsyld, Tessa Munkeboe; Eisum, Anne-Sofie Vibæk; Fornander, Freja; Buch, Astrid Emilie; Stemmerik, M.; Ruiz-Ruiz, Cristina; Krag, Thomas; Vissing, John

doi:10.1016/j.mito.2019.10.005

Cited by 41 publications

(42 citation statements)

References 18 publications

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“…At structural levels, p53 directly in uences mitochondrial respiration and impairs clearance of defective mitochondria [27,28], leading to mitochondrial dysfunction, a well-known driver of biologic ageing [29]. Consistently, emerging studies have proposed GDF-15 as a speci c biomarker of mitochondrial disorder [30,31]. In further support of GDF-15 as a marker of ageing, GDF-15…”

Section: Discussionmentioning

confidence: 88%

Growth differentiation factor-15 is a biomarker for all-cause mortality but less evident for cardiovascular outcomes: A prospective study

Bao

Borné

et al. 2021

American Heart Journal

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Section: Discussionmentioning

confidence: 88%

Growth differentiation factor-15 is a biomarker for all-cause mortality but less evident for cardiovascular outcomes: A prospective study

Bao

Borné

et al. 2021

American Heart Journal

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“…Increased serum GDF-15 levels have been associated with MD originated by different mutations and clinical conditions [21][22][23][24]. In different cohorts of MD patients, GDF-15 positively correlated with FGF-21, but usually showing a higher sensitivity for MD diagnosis than the latter [23,[25][26][27]. Notably, GDF-15 levels also increase as a response to stress and inflammation, and as a result, the blood concentration of GDF-15 is elevated in a variety of cardiovascular diseases, including heart failure and atherosclerosis, as well as in insulin resistance, renal insufficiency [28], and multiple sclerosis [29].…”

Section: Introductionmentioning

confidence: 99%

Plasma Gelsolin Reinforces the Diagnostic Value of FGF-21 and GDF-15 for Mitochondrial Disorders

Peñas

Torre

Laine-Menéndez

et al. 2021

IJMS

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Mitochondrial disorders (MD) comprise a group of heterogeneous clinical disorders for which non-invasive diagnosis remains a challenge. Two protein biomarkers have so far emerged for MD detection, FGF-21 and GDF-15, but the identification of additional biomarkers capable of improving their diagnostic accuracy is highly relevant. Previous studies identified Gelsolin as a regulator of cell survival adaptations triggered by mitochondrial defects. Gelsolin presents a circulating plasma isoform (pGSN), whose altered levels could be a hallmark of mitochondrial dysfunction. Therefore, we investigated the diagnostic performance of pGSN for MD relative to FGF-21 and GDF-15. Using ELISA assays, we quantified plasma levels of pGSN, FGF-21, and GDF-15 in three age- and gender-matched adult cohorts: 60 genetically diagnosed MD patients, 56 healthy donors, and 41 patients with unrelated neuromuscular pathologies (non-MD). Clinical variables and biomarkers’ plasma levels were compared between groups. Discrimination ability was calculated using the area under the ROC curve (AUC). Optimal cut-offs and the following diagnostic parameters were determined: sensitivity, specificity, positive and negative predictive values, positive and negative likelihood ratios, and efficiency. Comprehensive statistical analyses revealed significant discrimination ability for the three biomarkers to classify between MD and healthy individuals, with the best diagnostic performance for the GDF-15/pGSN combination. pGSN and GDF-15 preferentially discriminated between MD and non-MD patients under 50 years, whereas FGF-21 best classified older subjects. Conclusion: pGSN improves the diagnosis accuracy for MD provided by FGF-21 and GDF-15.

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“…The study sample included 18 recreational male athletes (mean ± SD age: 41.7 ± 5.0 years, BMI: 23.6 ± 1.8). Sample size was dependent on availability of volunteers and was not based on power calculations; however, sample size was in the range of that resulting from power calculations in studies of individuals at rest and after a single bout of exercise (Yatsuga et al, 2015;Poulsen et al, 2020). The median (interquartile range, IQR) years of training was 7 (5-11) years and the median (IQR) of weekly training hours was 6 (5-8) h/week.…”

Section: Methodsmentioning

confidence: 99%

Altered GDF15 and FGF21 Levels in Response to Strenuous Exercise: A Study in Marathon Runners

et al. 2020

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Background: Recreational marathon runners face strong physiological challenges. Assessment of potential biomarkers for the biological responses of runners will help to discriminate individual race responsiveness and their physiological consequences. This study sought to analyze the changes in the plasma levels of GDF15 and FGF21, novel endocrine factors related to metabolic stress, in runners following the strenuous exercise of a marathon race. Methods: Blood samples were obtained from eighteen male runners (mean ±SD, age: 41.7 ±5.0 years, BMI: 23.6 ± 1.8) 48 h before, immediately after, and 48 h after a marathon race, and from age-matched sedentary individuals. The level of GDF15, FGF21, and 38 additional biochemical and hematological parameters were determined. Results: The basal levels of GDF15 and FGF21 did not differ between runners before the race and sedentary individuals. Significant increases in the mean levels of GDF15 (4.2-fold) and FGF21 (20-fold) were found in runners immediately after the race. The magnitudes of these increases differed markedly among individuals and did not correlate with each other. The GDF15 and FGF21 levels had returned to the basal level 48 h postrace. The post-race value of GDF15 (but not FGF21) correlated positively with increased total white cell count (r = 0.50, P = 0.01) and neutrophilia (r = 0.10, P = 0.01). Conclusion: GDF15 and FGF21 are transiently increased in runners following a marathon race. The induction of GDF15 levels is associated with alterations in circulating immune cells levels.

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Growth and differentiation factor 15 as a biomarker for mitochondrial myopathy

Cited by 41 publications

References 18 publications

Growth differentiation factor-15 is a biomarker for all-cause mortality but less evident for cardiovascular outcomes: A prospective study

Growth differentiation factor-15 is a biomarker for all-cause mortality but less evident for cardiovascular outcomes: A prospective study

Plasma Gelsolin Reinforces the Diagnostic Value of FGF-21 and GDF-15 for Mitochondrial Disorders

Altered GDF15 and FGF21 Levels in Response to Strenuous Exercise: A Study in Marathon Runners

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