Abstract
The purpose of this study is to analyze the role of genes known to influence muscle performances on the outcome after enzyme replacement treatment (ERT) in type II Glycogenosis (GSDII). We analyzed 16 patients receiving ERT for ≥ two years. We assessed the changes in muscle strength by hand-held dynamometry, muscle mass by quantitative MRI, and resistance to exercise by the 6-minute walking test. Exercise gene assessment included angiotensin converting enzyme insertion/deletion polymorphism (ACE), alpha-actinin3 R577X polymorphism (ACTN3), and peroxisome proliferator activated receptor alpha G/C polymorphism (PPARα). Independent of disease severity, one third of patients had a poor response to ERT, which was found to be associated with ACE DD genotype. The ACTN3 null polymorphism appeared to exert a positive effect on treatment efficacy, while PPARα did not seem to exert any influence at all. We conclude that poor treatment outcome in ACE DD genotypes is in line with previous observation of a worse disease course in this subpopulation, and suggests the need for a more careful follow-up and individualized treatment approaches for these patients. Exercise genes may provide a new opportunity for studying the outcome after treatment and the muscle regeneration abilities in other models of genetic myopathies.
| Original language | English |
|---|---|
| Pages (from-to) | 104-110 |
| Number of pages | 7 |
| Journal | Molecular Genetics and Metabolism |
| Volume | 107 |
| Issue number | 1-2 |
| DOIs | |
| Publication status | Published - Sep 2012 |
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Keywords
- Enzyme replacement therapy
- Genetic polymorphisms
- Glycogen storage disease type II
- Volumetric MRI
ASJC Scopus subject areas
- Biochemistry
- Molecular Biology
- Genetics
- Endocrinology
- Endocrinology, Diabetes and Metabolism
Cite this
Can genes influencing muscle function affect the therapeutic response to enzyme replacement therapy (ERT) in late-onset Type II Glycogenosis? / Ravaglia, Sabrina; De Filippi, Paola; Pichiecchio, Anna; Ponzio, Michela; Saeidi Garaghani, Kolsoum; Poloni, Guy Umberto; Bini, Paola; Danesino, Cesare.
In: Molecular Genetics and Metabolism, Vol. 107, No. 1-2, 09.2012, p. 104-110.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Can genes influencing muscle function affect the therapeutic response to enzyme replacement therapy (ERT) in late-onset Type II Glycogenosis?
AU - Ravaglia, Sabrina
AU - De Filippi, Paola
AU - Pichiecchio, Anna
AU - Ponzio, Michela
AU - Saeidi Garaghani, Kolsoum
AU - Poloni, Guy Umberto
AU - Bini, Paola
AU - Danesino, Cesare
PY - 2012/9
Y1 - 2012/9
N2 - The purpose of this study is to analyze the role of genes known to influence muscle performances on the outcome after enzyme replacement treatment (ERT) in type II Glycogenosis (GSDII). We analyzed 16 patients receiving ERT for ≥ two years. We assessed the changes in muscle strength by hand-held dynamometry, muscle mass by quantitative MRI, and resistance to exercise by the 6-minute walking test. Exercise gene assessment included angiotensin converting enzyme insertion/deletion polymorphism (ACE), alpha-actinin3 R577X polymorphism (ACTN3), and peroxisome proliferator activated receptor alpha G/C polymorphism (PPARα). Independent of disease severity, one third of patients had a poor response to ERT, which was found to be associated with ACE DD genotype. The ACTN3 null polymorphism appeared to exert a positive effect on treatment efficacy, while PPARα did not seem to exert any influence at all. We conclude that poor treatment outcome in ACE DD genotypes is in line with previous observation of a worse disease course in this subpopulation, and suggests the need for a more careful follow-up and individualized treatment approaches for these patients. Exercise genes may provide a new opportunity for studying the outcome after treatment and the muscle regeneration abilities in other models of genetic myopathies.
AB - The purpose of this study is to analyze the role of genes known to influence muscle performances on the outcome after enzyme replacement treatment (ERT) in type II Glycogenosis (GSDII). We analyzed 16 patients receiving ERT for ≥ two years. We assessed the changes in muscle strength by hand-held dynamometry, muscle mass by quantitative MRI, and resistance to exercise by the 6-minute walking test. Exercise gene assessment included angiotensin converting enzyme insertion/deletion polymorphism (ACE), alpha-actinin3 R577X polymorphism (ACTN3), and peroxisome proliferator activated receptor alpha G/C polymorphism (PPARα). Independent of disease severity, one third of patients had a poor response to ERT, which was found to be associated with ACE DD genotype. The ACTN3 null polymorphism appeared to exert a positive effect on treatment efficacy, while PPARα did not seem to exert any influence at all. We conclude that poor treatment outcome in ACE DD genotypes is in line with previous observation of a worse disease course in this subpopulation, and suggests the need for a more careful follow-up and individualized treatment approaches for these patients. Exercise genes may provide a new opportunity for studying the outcome after treatment and the muscle regeneration abilities in other models of genetic myopathies.
KW - Enzyme replacement therapy
KW - Genetic polymorphisms
KW - Glycogen storage disease type II
KW - Volumetric MRI
UR - http://www.scopus.com/inward/record.url?scp=84866180231&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84866180231&partnerID=8YFLogxK
U2 - 10.1016/j.ymgme.2012.05.016
DO - 10.1016/j.ymgme.2012.05.016
M3 - Article
VL - 107
SP - 104
EP - 110
JO - Molecular Genetics and Metabolism
JF - Molecular Genetics and Metabolism
SN - 1096-7192
IS - 1-2
ER -