Dataset Information

Association of Myostatin Gene Polymorphisms with Strength and Muscle Mass in Athletes: A Systematic Review and Meta-Analysis of the MSTN rs1805086 Mutation.

ABSTRACT: Polymorphism (rs1805086), c.458A>G, p.Lys(K)153Arg(R), (K153R) of the myostatin gene (MSTN) has been associated with a skeletal muscle phenotype (hypertrophic response in muscles due to strength training). However, there are not enough reliable data to demonstrate whether MSTN rs1805086 K and R allelic variants are valid genetic factors that can affect the strength phenotype of athletes' skeletal muscles. The aim is to conduct a systematic review and meta-analysis of the association of MSTN rs1805086 polymorphism with the strength phenotype of athletes. This study analyzed 71 research articles on MSTN and performed a meta-analysis of MSTN K153R rs1805086 polymorphism in strength-oriented athletes and a control (non-athletes) group. It was found that athletes in the strength-oriented athlete group had a higher frequency of the R minor variant than that in the control group (OR = 2.02, P = 0.05). Thus, the obtained results convincingly demonstrate that there is an association between the studied polymorphism and strength phenotype of athletes; therefore, further studies on this association are scientifically warranted.

SUBMITTER: Kruszewski M

PROVIDER: S-EPMC9690375 | biostudies-literature | 2022 Nov

REPOSITORIES: biostudies-literature

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Association of Myostatin Gene Polymorphisms with Strength and Muscle Mass in Athletes: A Systematic Review and Meta-Analysis of the MSTN rs1805086 Mutation.

Kruszewski Marek M Aksenov Maksim Olegovich MO

Genes 20221107 11

Polymorphism (rs1805086), c.458A>G, p.Lys(K)153Arg(R), (K153R) of the myostatin gene (MSTN) has been associated with a skeletal muscle phenotype (hypertrophic response in muscles due to strength training). However, there are not enough reliable data to demonstrate whether MSTN rs1805086 K and R allelic variants are valid genetic factors that can affect the strength phenotype of athletes' skeletal muscles. The aim is to conduct a systematic review and meta-analysis of ...[more]

PMID: 36360291

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Project description:BackgroundGrowth differentiation factor 11 (GDF11) is a member of the transforming growth factor β superfamily. The GDF11 propeptide, which is derived from the GDF11 precursor protein, blocks the activity of GDF11 and its homolog, myostatin, which are both potent inhibitors of muscle growth. Thus, treatment with GDF11 propeptide may be a potential therapeutic strategy for diseases associated with muscle atrophy like sarcopenia and the muscular dystrophies. Here, we evaluate the impact of GDF11 propeptide-Fc (GDF11PRO-Fc) gene delivery on skeletal muscle in normal and dystrophic adult mice.MethodsA pull-down assay was used to obtain physical confirmation of a protein-protein interaction between GDF11PRO-Fc and GDF11 or myostatin. Next, differentiated C2C12 myotubes were treated with AAV6-GDF11PRO-Fc and challenged with GDF11 or myostatin to determine if GDF11PRO-Fc could block GDF11/myostatin-induced myotube atrophy. Localized expression of GDF11PRO-Fc was evaluated via a unilateral intramuscular injection of AAV9-GDF11PRO-Fc into the hindlimb of C57BL/6J mice. In mdx mice, intravenous injection of AAV9-GDF11PRO-Fc was used to achieve systemic expression. The impact of GDF11PRO-Fc on muscle mass, function, and pathological features were assessed.ResultsGDF11PRO-Fc was observed to bind both GDF11 and myostatin. In C2C12 myotubes, expression of GDF11PRO-Fc was able to mitigate GDF11/myostatin-induced atrophy. Following intramuscular injection in C57BL/6J mice, increased grip strength and localized muscle hypertrophy were observed in the injected hindlimb after 10 weeks. In mdx mice, systemic expression of GDF11PRO-Fc resulted in skeletal muscle hypertrophy without a significant change in cardiac mass after 12 weeks. In addition, grip strength and rotarod latency time were improved. Intramuscular fibrosis was also reduced in treated mdx mice; however, there was no change seen in central nucleation, membrane permeability to serum IgG or serum creatine kinase levels.ConclusionsGDF11PRO-Fc induces skeletal muscle hypertrophy and improvements in muscle strength via inhibition of GDF11/myostatin signaling. However, GDF11PRO-Fc does not significantly improve the dystrophic pathology in mdx mice.

Dataset Information

Association of Myostatin Gene Polymorphisms with Strength and Muscle Mass in Athletes: A Systematic Review and Meta-Analysis of the MSTN rs1805086 Mutation.

Publications

Association of Myostatin Gene Polymorphisms with Strength and Muscle Mass in Athletes: A Systematic Review and Meta-Analysis of the MSTN rs1805086 Mutation.

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