Polymorphism in exercise genes and respiratory function in Late Onset Pompe Disease (LOPD)

Sabrina Ravaglia, Alberto Malovini, Serena Cirio, Cesare Danesino, Paola de Filippi, Maurizio Moggio, Tiziana Mongini, Lorenzo Maggi, Serena Servidei, Andrea Vianello, Antonio Toscano, Paola Tonin, Maria Antonietta Maioli, Rossella Parini, Massimiliano Filosto, Grazia Crescimanno, Sebastiano Arceri, Manuela Piran, Annalisa Carlucci

Research output: Contribution to journalArticlepeer-review


BACKGROUND: Genetic polymorphisms influencing muscle structure and metabolism may affect the phenotype of metabolic myopathies. We here analyze the possible influence of a wide panel of "exercise genes" on the severity and progression of respiratory dysfunction in LOPD. We stratified patients with comparable age and disease duration according to the severity of their respiratory phenotype, assessed by both upright FVC% and postural drop in FVC%.

METHODS: We included 43 LOPD patients (25 males, age 50.8+13.6 years) with a two-year follow-up since the beginning of ERT. Twenty-two patients showed a postural drop > 25% T0, seven other developed it during the follow-up. We analyzed the relationship between the progression of respiratory dysfunction and genetic polymorphisms affecting muscle function and structure (ACE, ACTN3, PPRalpha, AGT), glycogen metabolism (GYS, GSK3b), autophagy (SIRT1, ATG7).

RESULTS: Individuals carrying two copies of the ACE D-allele shared a 24-fold increase in the risk of severe respiratory dysfunction and progression during the two-year follow-up. ACTN3-XX polymorphism was also associated with worse respiratory outcome.

CONCLUSION: The study of exercise genes is of particular interest in respiratory muscles, due to their peculiar features, i.e. continuous, low-intensity contraction, and prominent recruitment of type I fibers. In line with previous observations on skeletal muscles, ACE-DD and ACTN3-XX genotypes were associated with indirect evidence of more severe respiratory phenotypes. On the contrary, polymorphisms related to autophagy and glycogen metabolism did not seem to influence respiratory muscles.

Original languageEnglish
JournalJournal of applied physiology (Bethesda, Md. : 1985)
Publication statusE-pub ahead of print - Nov 4 2021


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