Myostatin as "bodybuilding gene" (brief overview)

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Dr.Hab., Associate Professor M.O. Aksenov1, 2
E.A. Krylasova2
PhD I.I. Starkova2
Postgraduate A.O. Zaitseva2
1Plekhanov Russian University of Economics, Moscow
2 Banzarov Buryat State University, Ulan-Ude

Corresponding author: aksenov.mo@rea.ru

Abstract

Objective of the study was to analyze the latest scientific research to identify associations of the K153R polymorphism in the myostatin (MSTN) gene (rs1805086) with skeletal muscle hypertrophy and athletes’ strength.

Methods and structure of the study. The research articles to be analyzed were searched in the databases of PubMed, WebofScience, eLIBRARY.ru, SNPedia, Wiley Online Library, and Europe PMC resource. The following keywords were used during the search: myostatin, MSTN, GDF-8, K153R, rs1805086. We compiled a list of publications about myostatin, including 81 scientific papers published in the above databases before February 2020. We used Clarivate Analytics’s EndNote Viever X9.2 software to analyze and systematize the publications.

Results and conclusions. Subject to the study were 94 healthy untrained Chinese males aged 8-22 years. The study showed that the increase in the biceps girth =0.300±0.131 cm and quadriceps girth =0.421±0.281 cm (p<0.01 for both muscle groups) was significantly higher in the subjects carrying the KR genotype, rather than in those carrying the KK genotypes of the K153R polymorphism in MSTN. Therefore, the data obtained prove that this polymorphism may not only promote the increase of muscle size in the absence of trainings but is also associated with a more pronounced increase in the muscle mass of the subjects carrying the R allele (arginine) after strength trainings. Hence, screening of this polymorphism can be considered as a genetic marker of sports selection in weightlifting sports (Li et al., 2014).

It is only in the past 15 years that genetic polymorphisms controlling the skeletal muscle mass and function in athletes, and the mechanisms of their manifestation within the phenotype have begun to be clarified. It is not surprising that new mechanisms and associations of these genes continue to be discovered, and indeed, there has recently been considerable progress in this area. Besides, the discovery of genes that significantly improve the aptitude for sports, such as myostatin, will significantly enhance the quality of sports selection and orientation.

Keywords: sports, training, systematic review, myostatin, skeletal muscles, gene, strength, athletic training, hypertrophy, MSTN, K153R, rs1805086.

Background. Since its initial discovery in 1997 (McPherron et al., 1997), myostatin (encoded by the MSTN gene) has made a significant progress in the study of various genetic factors of strength development of athletes. The MSTN gene is located on the long arm (q) of chromosome 2 at position 32.2 (2q32.2); more than 260 polymorphisms have been described to date in its sequence; it occupies a region of about 8 kb, and has 3 exons (Rodriguez et al., 2014). It was found that mutations in the MSTN gene lead to a significant increase in muscle mass (Kollias and McDermott, 2008). MSTN is an important gene that affects myogenesis and plays a key role in the process of regulation of muscle tissue growth and differentiation (McFarlane et al., 2011). In particular, the genetic predisposition to muscle mass gain is due to the decreased myostatin expression and is an advantage in the display of strength abilities in sports (Ferrell et al., 1999).

This gene was named myostatin for its ability to inhibit muscle tissue differentiation and growth (Yamada et al., 2012), while increased myostatin expression was associated with muscle atrophy (Dalbo et al., 2011). Together, these studies confirmed the central, decisive role of myostatin in muscle growth inhibition (Allen et al., 2011; Zheng et al., 2019).

Earlier studies showed that a number of missense mutations in exons 1 and 2 of the MSTN gene (A55T, K153R, E164K, P198A, and I225T) are of the main interest in confirming the association between athletes’ strength and muscle hypertrophy (Thomis et al., 2004). Of particular interest is the K153R polymorphism in this gene (Garatachea et al., 2013; Gonzalez-Freire et al., 2010; Santiago et al., 2011).

Objective of the study was to analyze the latest scientific research to identify associations of the K153R polymorphism in the myostatin (MSTN) gene (rs1805086) with skeletal muscle hypertrophy and athletes’ strength.

Methods and structure of the study. The research articles to be analyzed were searched in the databases of PubMed, WebofScience, eLIBRARY.ru, SNPedia, Wiley Online Library, and Europe PMC resource. The following keywords were used during the search: myostatin, MSTN, GDF-8, K153R, rs1805086. We compiled a list of publications about myostatin, including 81 scientific papers published in the above databases before February 2020. We used Clarivate Analytics’s EndNote Viever X9.2 software to analyze and systematize the publications.

Results and discussion. Subject to the study were 94 healthy untrained Chinese males aged 8-22 years. The study showed that the increase in the biceps girth =0.300±0.131 cm and quadriceps girth =0.421±0.281 cm (p<0.01 for both muscle groups) was significantly higher in the subjects carrying the KR genotype, rather than in those carrying the KK genotypes of the K153R polymorphism in MSTN. Therefore, the data obtained prove that this polymorphism may not only promote the increase of muscle size in the absence of trainings but is also associated with a more pronounced increase in the muscle mass of the subjects carrying the R allele (arginine) after strength trainings. Hence, screening of this polymorphism can be considered as a genetic marker of sports selection in weightlifting sports (Li et al., 2014).

Santiago C., Ruiz J.R., Rodríguez-Romo G., et al. (2011) studied the associations between the K153R polymorphism in MSTN and explosive strength of the legs, and managed to prove that in untrained males, the K153R polymorphism in MSTN is associated with the ability to produce "peak" power during muscle contractions, as assessed in the vertical jump test. The authors reported that of the identified MSTN variations in humans, the Lys (K) 153Arg® polymorphism located in exon 2 (rs1805086, 2379 A>G replacement) is a candidate to affect skeletal muscle phenotypes. The Lys (K) 153Arg® amino acid replacement is found within the active mature peptide of the MSTN protein; it could theoretically influence proteolytic processing with its propeptide, or affinity to bind with the extracellular activin type II receptor (ActRIIB), which in turn induces myoblast proliferation and differentiation, as well as muscle mass.

According to the authors, the frequency of the mutant R allele was about 3-4% in the Chinese males, with the frequency of mutant homozygotes (RR) below 1%, which definitely prevents from studying large groups of people carrying the R variant, especially in sports.

The authors found that the existing data on MSTN K153R polymorphisms and human muscle phenotypes give contradictory results (Seibert et al., 2001). A number of studies indicated a significant effect of the MSTN variants and muscle mass response to strength trainings regardless of gender. The 153R allele was associated with a larger muscle hypertrophic response to training loads (Ivey et al., 2000).

Ivey F.M., Roth S.M., Ferrell R.E., et al. reported that the K153R genotype of MSTN tended to affect the hypertrophic reaction of the skeletal muscles of heterozygous females to strength trainings. The experiments proved that the increase in the leg muscle mass in response to strength trainings was 68% higher in the females carrying the KR genotype than in those carrying the KK genotype (P=0.056) (Ivey et al., 2000). These data indicate that the K153R rare allele plays an important role in the hypertrophic muscle response. The authors noted that more research is still needed on the Lys 153 Arg allele in the human myostatin gene in the muscle response to strength trainings, especially in females with large body mass.

Ferrell R.E. et al. did not found a single person with the RR genotype of MSTN among the Caucasians engaged in strength sports (Ferrell et al., 1999). However, the authors stated that the A55T and K153R variants may affect the functions of the gene products and the distribution of nutrients in humans, both heterozygous and homozygous to the rare allele, which, in turn, can manifest itself in the phenotypic signs of the body associated with the increase in muscle mass in response to strength trainings. As in any other study, the authors pointed out the need for further study of this polymorphism.

Conclusion. It is only in the past 15 years that genetic polymorphisms controlling the skeletal muscle mass and function in athletes, and the mechanisms of their manifestation within the phenotype have begun to be clarified. It is not surprising that new mechanisms and associations of these genes continue to be discovered, and indeed, there has recently been considerable progress in this area. Besides, the discovery of genes that significantly improve the aptitude for sports, such as myostatin, will significantly enhance the quality of sports selection and orientation.

The study was performed with the financial support from the Russian Foundation for Basic Research and the Republic of Buryatia under Project No. 18-413-030001.

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Information for contacting the author: aksenov.mo@rea.ru

Submitted for publication on June 20, 2020