학술논문
The IAAM LTBP4 Haplotype is Protective Against Dystrophin-Deficient Cardiomyopathy.
Document Type
article
Author
Bello, Luca; Sabbatini, Daniele; Fusto, Aurora; Gorgoglione, Domenico; Borin, Giovanni; Penzo, Martina; Riguzzi, Pietro; Villa, Matteo; Vianello, Sara; Calore, Chiara; Melacini, Paola; Vio, Riccardo; Barp, Andrea; DAngelo, Grazia; Gandossini, Sandra; Politano, Luisa; Berardinelli, Angela; Messina, Sonia; Vita, Gian; Pedemonte, Marina; Bruno, Claudio; Albamonte, Emilio; Sansone, Valeria; Baranello, Giovanni; Masson, Riccardo; Astrea, Guja; DAmico, Adele; Bertini, Enrico; Pane, Marika; Lucibello, Simona; Mercuri, Eugenio; Spurney, Christopher; Clemens, Paula; Morgenroth, Lauren; Gordish-Dressman, Heather; Hoffman, Eric; Pegoraro, Elena; McDonald, Craig
Source
Journal of Neuromuscular Diseases. 11(2)
Subject
Language
Abstract
BACKGROUND: Dilated cardiomyopathy (DCM) is a major complication of, and leading cause of mortality in Duchenne muscular dystrophy (DMD). Its severity, age at onset, and rate of progression display wide variability, whose molecular bases have been scarcely elucidated. Potential DCM-modifying factors include glucocorticoid (GC) and cardiological treatments, DMD mutation type and location, and variants in other genes. METHODS AND RESULTS: We retrospectively collected 3138 echocardiographic measurements of left ventricular ejection fraction (EF), shortening fraction (SF), and end-diastolic volume (EDV) from 819 DMD participants, 541 from an Italian multicentric cohort and 278 from the Cooperative International Neuromuscular Group Duchenne Natural History Study (CINRG-DNHS). Using generalized estimating equation (GEE) models, we estimated the yearly rate of decrease of EF (-0.80%) and SF (-0.41%), while EDV increase was not significantly associated with age. Utilizing a multivariate generalized estimating equation (GEE) model we observed that mutations preserving the expression of the C-terminal Dp71 isoform of dystrophin were correlated with decreased EDV (-11.01 mL/m2, p = 0.03) while for dp116 were correlated with decreased EF (-4.14%, p =