High prevalence of plasma lipid abnormalities in human and canine Duchenne and Becker muscular dystrophies depicts a new type of primary genetic dyslipidemia.
Duchenne muscular dystrophy
LDL
Muscle wasting
Triglycerides
plasma
Journal
Journal of clinical lipidology
ISSN: 1933-2874
Titre abrégé: J Clin Lipidol
Pays: United States
ID NLM: 101300157
Informations de publication
Date de publication:
Historique:
received:
28
01
2020
revised:
13
05
2020
accepted:
15
05
2020
pubmed:
1
7
2020
medline:
7
8
2021
entrez:
29
6
2020
Statut:
ppublish
Résumé
Duchenne muscular dystrophy (DMD) and Becker muscular dystrophy (BMD) are allelic X-linked recessive muscle diseases caused by mutations in the DMD gene, with DMD being the more severe form. We have recently shown that increased plasma low-density lipoprotein-associated cholesterol causes severe muscle wasting in the mdx mouse, a mild DMD model, which suggested that plasma lipids may play a critical role in DMD. We have also observed that loss of dystrophin in mice causes unexpected elevations in plasma lipoprotein levels. The objectives of the study were to determine whether patients with DMD and BMD also present with clinically relevant plasma lipoprotein abnormalities and to mitigate the presence of confounders (medications and lifestyle) by analyzing the plasma from patients with DMD/BMD and unmedicated dogs with DMD, the most relevant model of DMD. Levels of low-density lipoprotein-associated cholesterol, high-density lipoprotein cholesterol, and triglycerides were analyzed in patients with DMD and BMD and female carriers. Samples from unmedicated, ambulatory dogs with DMD, unaffected carriers, and normal controls were also analyzed. We report that 97% and 64% of all pediatric patients with DMD (33 of 36) and BMD (6 of 11) are dyslipidemic, along with an unusually high incidence in adult patients with BMD. All dogs with DMD showed plasma lipid abnormalities that progressively worsened with age. Most strikingly, unaffected carrier dogs also showed plasma lipid abnormalities similar to affected dogs with DMD. Dyslipidemia is likely not secondary to liver damage as unaffected carriers showed no plasma aminotransferase elevation. The high incidence of plasma lipid abnormalities in dystrophin-deficient plasma may depict a new type of genetic dyslipidemia. Abnormal lipid levels in dystrophinopathic samples in the absence of muscle damage suggest a primary state of dyslipidemia. Whether dyslipidemia plays a causal role in patients with DMD warrants further investigation, which could lead to new diagnostic and therapeutic options.
Sections du résumé
BACKGROUND
Duchenne muscular dystrophy (DMD) and Becker muscular dystrophy (BMD) are allelic X-linked recessive muscle diseases caused by mutations in the DMD gene, with DMD being the more severe form. We have recently shown that increased plasma low-density lipoprotein-associated cholesterol causes severe muscle wasting in the mdx mouse, a mild DMD model, which suggested that plasma lipids may play a critical role in DMD. We have also observed that loss of dystrophin in mice causes unexpected elevations in plasma lipoprotein levels.
OBJECTIVE
The objectives of the study were to determine whether patients with DMD and BMD also present with clinically relevant plasma lipoprotein abnormalities and to mitigate the presence of confounders (medications and lifestyle) by analyzing the plasma from patients with DMD/BMD and unmedicated dogs with DMD, the most relevant model of DMD.
METHODS
Levels of low-density lipoprotein-associated cholesterol, high-density lipoprotein cholesterol, and triglycerides were analyzed in patients with DMD and BMD and female carriers. Samples from unmedicated, ambulatory dogs with DMD, unaffected carriers, and normal controls were also analyzed.
RESULTS
We report that 97% and 64% of all pediatric patients with DMD (33 of 36) and BMD (6 of 11) are dyslipidemic, along with an unusually high incidence in adult patients with BMD. All dogs with DMD showed plasma lipid abnormalities that progressively worsened with age. Most strikingly, unaffected carrier dogs also showed plasma lipid abnormalities similar to affected dogs with DMD. Dyslipidemia is likely not secondary to liver damage as unaffected carriers showed no plasma aminotransferase elevation.
CONCLUSIONS
The high incidence of plasma lipid abnormalities in dystrophin-deficient plasma may depict a new type of genetic dyslipidemia. Abnormal lipid levels in dystrophinopathic samples in the absence of muscle damage suggest a primary state of dyslipidemia. Whether dyslipidemia plays a causal role in patients with DMD warrants further investigation, which could lead to new diagnostic and therapeutic options.
Identifiants
pubmed: 32593511
pii: S1933-2874(20)30196-3
doi: 10.1016/j.jacl.2020.05.098
pmc: PMC7492428
mid: NIHMS1598886
pii:
doi:
Substances chimiques
Lipids
0
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, N.I.H., Intramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
459-469.e0Subventions
Organisme : NIAMS NIH HHS
ID : R01 AR070517
Pays : United States
Organisme : NINDS NIH HHS
ID : R01 NS090634
Pays : United States
Organisme : CIHR
ID : PJT159511
Pays : Canada
Organisme : Medical Research Council
Pays : United Kingdom
Informations de copyright
Copyright © 2020 National Lipid Association. Published by Elsevier Inc. All rights reserved.
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