Key result
Elevated circulating miR-222 was identified as a significant independent predictor for the presence of myocardial scarring in patients with muscular dystrophy (OR 938).
Cross-Sectional (n=89)
No
Circulating miRNAs miR-222, miR-26a, and miR-378a-5p are upregulated in muscular dystrophy patients with myocardial scarring and may serve as novel biomarkers for structural cardiac alterations.
Hypothesis-generating for miR-222 as a scarring biomarker in muscular dystrophy; prospective validation required before clinical consideration.
BACKGROUND: Duchenne and Becker muscular dystrophy (DMD and BMD) are X-chromosomal recessive neuromuscular disorders that are caused by mutations in the dystrophin gene and characterized by cardiac involvement. Circulating microRNAs (miRNAs) have been proposed as diagnostic biomarkers for various cardiovascular diseases. However, circulating miRNAs reflecting the presence and/or disease severity of cardiac involvement in DMD/BMD patients have not been described so far. METHODS: Sixty-three male patients with known MD and 26 age-matched healthy male controls were prospectively enrolled. All MD patients and controls underwent comprehensive cardiovascular magnetic resonance (CMR) studies as well as venous blood sampling on the same day. RESULTS: An impaired left ventricular (LV) systolic function (defined as LV-EF <55 %) was detected in 29 (46 %) and presence of late gadolinium enhancement (LGE) indicative of myocardial fibrosis in 48 (76 %) MD patients with an exclusively non-ischemic pattern. Whereas no significant differences were observed for the 27 selected circulating miRNAs in MD patients with abnormal CMR findings (comprising structural and/or functional impairments) compared to those with completely normal CMR studies, a significant up-regulation of three miRNAs was observed in LGE-positive MD patients compared to LGE-negative ones: miR-222 (1.8-fold, p = 0.035), miR-26a (2.1-fold, p = 0.03) and miR-378a-5p (2.4-fold, p = 0.026). A signature of these three miRNAs (miR-26a, miR-222 and miR-378a-5p) resulted in an area under the curve (AUC) value of 0.74 for the diagnosis of LGE-positive MD patients. In a multivariable model, three independent predictors for LGE presence were identified comprising not only clinical and laboratory markers (LV-EF: OR 0.47, 95 % CI 0.24-0.89, p = 0.021 and elevated hs-Trop: OR 2559, 95 % CI 2.97-22.04*10(5), p = 0.023) but also the circulating miR-222 (OR 938, 95 % CI 938.46, 3.56-24.73*10(4), p = 0.016). CONCLUSIONS: Up-regulation of circulating miRNAs miR-222, miR-26a and miR-378a-5p indicates the presence of myocardial scars in MD patients. Plasma miR-222 appears to be a promising novel biomarker reflecting structural - but not functional - cardiac alterations in MD patients.
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Florian et al. (2016) conducted a cross-sectional in Duchenne and Becker muscular dystrophy (DMD and BMD) (n=89). Elevated circulating miR-222 vs. Lower circulating miR-222 was evaluated on Presence of late gadolinium enhancement (LGE) indicative of myocardial scarring (OR 938, 95% CI 3.56-24.73*10 4, p=0.016). Elevated circulating miR-222 was identified as a significant independent predictor for the presence of myocardial scarring in patients with muscular dystrophy (OR 938).
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