Research ArticleAbstract
Introduction: The high incidence of sports injuries in elite athletes is a concern in sports medicine, a broad vision of sport injuries in Colombia and its pathophysiology can be achieved in the scope of genomics, which could respond to numerous sports injuries from the Identification of single nucleotide polymorphism that affect the health of athletes and often distance them from the field of play.
Objective: To determine the incidence of nucleotide polymorphisms (SNPs) in sports injuries of weightlifters. Material and methods. We searched in the databases PubMed, ScienceDirect and EBSCO for studies experimental published to January 2020, including studies in English and Portuguese, corresponding to case-control clinical studies, where the experimental group were weightlifters and controls were supposedly healthy people. The final papers were assessed for quality and bias using the Jadad scoring scale or Oxford quality scoring system. From the data obtained, heterogeneity was identified with the I2 test and the Q statistic, for the estimation of the effect in the cohort studies the odds ratio (OR) and P value <0.05 were used, obtaining the forest plots of each gen. Results. 4 out of 1220 studies were selected, finding a degree of heterogeneity in all studies, such as the risk of injury for the SNPs of the ACNT3 and COL5A1 genes.
Conclusion: The existence of genetic polymorphisms interacts in the integrity of the muscular and tendon system, which allows the incidence of sports injury in weightlifters to be higher, as well as the need to delve into the subject from the prevention of injury and health promotion in elite athletes.
Keywords: Injuries; Genetic Polymorphism; ACTN3; COL5A1 (DeCS source)
Introduction
Since the advances that have been generated with the analysis
of the human genome [1], various studies propose the explanation
of multiple pathologies with the presence of Single Nucleotide
Polymorphisms (SNPs), that is why research was sought to link
certain SNPs with sports injuries in weightlifters and, from this,
obtain a clear basis for conducting an exploratory study in a
population of athletes who presented sports injuries. Olympic
weightlifting are the most commonly practiced strength sports
where maximal strength in one repetition is the primary focus. In
weightlifting there are two events: the snatch and the clean and
jerk. Powerlifting consists of three events: the squat, bench press
and deadlift. The goal of sports is to lift the maximum weight in
each event [2]. Sports injuries have been described as acute,
being common in weight training such as sprains, strains, tendon
avulsions, and compartment syndromes. Common chronic injuries
have also been characterized, including rotator cuff tendinopathy
and stress injuries in the vertebrae, clavicles, and upper extremities
[3]. The origins of sports injuries are diverse; some authors cite
physical and physiological factors that are associated with lifestyle
habits such as diet and sleep; others indicate that injuries are
associated with age, sex, the training process, and fatigue [4].
Currently, information on the frequency and location of sports injuries in weightlifters is limited, and even more so when studying
the presence of single nucleotide polymorphisms associated with
sports injuries in weightlifters.
The studies by Rodas et al. [5], cite a high tendency for injuries
in a competition, of which 30 to 40% are of muscular origin, which
implies an injury risk of almost 2 per 1,000 hours of exposure
[6], in the same way, other studies report between 50 and 60%
of injuries related to the articular and ligament system [7].
Undoubtedly, the constant physical exercise in high performance
athletes generates adaptations and changes in their physiological
functions [8], that result in metabolic adjustments, which impact
the cardiac and pulmonary systems, among others. At a molecular
level, this is evident in the phenotypic changes of soft tissues [9],
accompanied by the activation or repression of specific signaling in
gene expression pathways [10], a relevant aspect when identifying
the high rate of sports injuries. Sports injuries depend largely on
external and internal factors [11], related to vulnerability to these
kind of injuries. External factors like the frequency of the exercise,
intensity, and workload [12] are overcome by designing a tailored
routine for the player. On the other hand, some intrinsic factors are
associated with genetic susceptibility [13], where several single
nucleotide polymorphisms (SNPs) are related. They are located in
genes responsible for encoding structural, and soft tissue regulatory
proteins that are involved in the lesions [14]. Some research
refers to genetic markers in relation to some parameters of sports
performance [15], where the relationship of the SNPs with various
pathologies as populations, an example of this are the ACTN genes
[16], COL1A1 [17], COL5A1 [18], a fact that led to the search for
relevant information on these genes with sports injuries and which
were taken into account for the performance of this meta-analysis.
SNPs contribute to inter-individual variations in the structural
and functional properties of muscle and tendon, which could be
involved the susceptibility of the lesion [19], this is how the literature
presents a series of SNPs associated with sports injuries in some
genes like ACTN3, a gene that encodes the α-actinin-3 protein, a
structural component of the Z disk where the thin filaments of actin
are anchored to keep the myofibrillar matrix of fast muscle fibers
[20]. Its absence affects the functionality of skeletal muscle when
strong contractions are generated [21]. One of the cases presented
in recent investigations with athletes of various modalities shows
that the SNPs R577 of the ACTN3 gene expresses the substitution of
a cytosine (C) for a thymine (T) at nucleotide number 1747 of the
DNA sequence in the exon 16, which replaces the synthesis of an
arginine with a stop codon [22], causing the production of a protein
of only 577 amino acids and thus generating two allele variants:
a functional R allele and a non-functional X allele [23,24]. Type V
collagen may be a structurally minor player in the collagen hierarchy
but is functionally prominent where it plays an important role in
regulating fiber diameter as well as assembly (fibrillogenesis)
of collagen fibers [25]. Type V collagen protein is encoded by the
collagen type V alpha 1 chain (COL5A1) gene, located on the long
(q) arm of chromosome 9 [26] and is expressed in both tendons
and ligaments. This leads us to review the bibliography related to
the association of single nucleotide polymorphisms (SNPs) with
sports injuries in soccer. The objective is to strengthen the field of
sports genomics, since it has been little explored in Colombia and
fundamental for the generation of personalized sports actions,
which would give the opportunity to direct preventive actions
and timely intervention to lessen the impact of injuries and thus
answer the research question about ¿what are the single nucleotide
polymorphisms associated with sports injuries in weightlifters?
Methods and Materials
A meta-analysis was carried out, according to the Preferred Reporting Items for Systematic Reviews and Meta- Analyses (PRISMA) guidelines [27]. The systematic review of the literature was done until January 2020, there were searched studies published in the last 6 years in the databases indexed in PubMed, ScienceDirect and EBSCO, taking into account that the latest relevant advances in sportomic were present since 2013 [28]. Additional publications were also considered by cross-referencing. Also, a manual search was carried out in the Pubmed databases for the references of the 5 selected articles that served as support for the study. It was used a combination of keywords to detect potentially relevant studies such as sports injury, muscle strain, muscle damage, sports trauma, sports genetics, weightlifters injury, polymorphisms or gene or SNPs, and genotype.
Study Selection
All publications retrieved were screened by title and any duplicates or those irrelevant to the research question were removed. Abstracts of the remaining studies were then similarly screened, and 4 studies were selected for full-text assessment against the predetermined inclusion and exclusion criteria outlined below.
Inclusion and Exclusion Criteria
The present review included case-control studies and genomic
association. To be included, the studies had to provide data on
the genotypes associated with the state of the population, whose
methodology will perform DNA extraction and quantification. The
studies should be written in English or Portuguese. There were no
restrictions applied regarding the age, gender, or ethnicity of the
participants.
Studies were excluded if they were:
a) review articles, congress abstracts, editorials or other
non-original articles
b) reported in a language other than English. Overall, 26
studies were included for qualitative synthesis. The study
selection process and reasons for exclusion are in Figure 1.
Data Extraction and Quality Assessment
For all selected studies, the following data were extracted:
a) name of first author
b) date of publication
c) characteristics of the participants
d) study design (Table 1).
Table 1: Characteristics in included Studies.
Risk of Bias Assessment Quality Evaluation
The risk of bias of individual studies was assessed using the
Cochrane Collaboration´s risk of bias tool [30]. Studies were given
an overall risk of bias grade of either “high”, “unclear” or “low”
calculated from the following five domains:
a) sequence generation
b) allocation concealment
c) blinding
d) Incomplete outcome data
e) selective reporting of results.
If details for a particular domain were insufficient, the risk of
bias was assessed as “unclear” (Table 2). Studies were assessed for
inclusion by autors, with disagreements resolved by discussion,
and arbitration from the third author if necessary. If a decision on
whether to include or exclude a paper could not be made from the
title and abstract, the full text was obtained and checked.
Table 2: Assessing risk of bias in included Studies.
Data
For the quality of the studies the Oxford quality scoring system was used [31,32]. This scale presents a quality score of five points. Additionally, it includes two criteria for an appropriate randomization method and stealth placement, which range from 0 (weak) to 5 (good) (Table 3). The analyzed studies presented a score of 4.1 points out of 5 was obtained, indicating that the studies have a higher quality than the expected average.
Table 3: Oxford Quality scoring system.
Statistical Analysis
The random-effects models were used to perform the metaanalysis using the free online software version of Cochrane Review Manager (RevMan) version 5.3. The degree of heterogeneity between the results of the study was evaluated with the statistical I2. The significant association between polymorphisms and sports injuries in soccer was estimated by odd relationships (OR) at a 95% confidence intervals (CI). The comparison of the soccer players with the controls of the healthy population was made with RevMan to build Forest Plot [33].
Results
Once the non-relevant articles were discarded, the PubMed, ScienceDirect, EBSCO databases were used with the cross combination of keywords: sports injury, muscle strain, muscle damage, sports trauma, sports genetics, polymorphisms or gene or SNP, genotype. Then, the inclusion criteria were designed as shown in Figure 1. The general characteristics of the 4 studies corresponding to the control and experimental groups are shown in Table 1. The random-effects model (Odds Ration) was used due to population heterogeneity. Below is the subgroup analysis performed according to the different polymorphisms found. The association between ACTN3 polymorphism, and the risk of sports injury is shown in Figure 2, whose heterogeneity is high (I2 of 61%), which leads to a risk of injury of OR 0.98, indicating that the risk of injury is greater in the healthy population, CI of 98% (0.64-1.50), statistically significant (P 0,03). The results show that the COL5A1, whose heterogeneity is high (I2 of 52%), which leads to a risk of injury of OR 0.98, indicating that the risk of injury is greater in the healthy population, CI of 95% (0.70-1.37), as shown in Figure 3.
Figure 1: The study selection process.
Figure 2: Forest Plot ACTN3.
Figure 3: Forest Plot COL5A1.
Discussion
The new sports genomics field focus on research of the SNPs of
the genes involved in sports injuries with the aim to evaluate the
correlation between a personalized workout with specific SNPs
combinations in high performance athletes. This approach is in
agreement with Sarzynski MA, Ghosh S, Bouchard [34], where it is
proposed to establish future training models, design, and plan sports
follow-up processes based on the present polymorphisms that have
a lower risk [35]. In general, this meta-analysis delimited which
polymorphisms in COL5A1 (rs12722) and ACTN3 (Rx577R) are
determinants for the analysis and relationship with sports injuries,
which gains importance in the diagnostic and treatment processes.
Genetic variations of the COL5A1 gene affect mRNA stability and
its export from the nucleus after transcription, where regulatory
sequences control gene expression at the post-transcriptional
level [36]. Therefore, mutations or variations of a single nucleotide
within this region can alter the secondary structure of mRNA and,
therefore, the characteristics of proteins [37]. leads to poorly
organized fibrils, decreased tensile strength, and reduced stiffness
of connective tissue [38]. Functionally, rs12722 variants are
believed to alter the stability of COL5A1 mRNA.
Alleles of the rs12722 SNP are proposed to have differential
effects on mRNA stability. Stiffness is a complex trait defined by the
mechanical property of tensile tissue to resist deformation without
failure the T allele is hypothesized to increase mRNA stability by
increasing the abundance of collagen V, reducing fibril diameter
and increasing tissue-fibril density and tissue stiffness. Previous
investigations have described the rs12722 variant genotype with
phenotype associations in chronic tendon pathology [39]. The
athletic population has a genetic variety being sport an important
epigenetic marker for the study [29-31]. This confirms that the
field of sports genetics still lacks some answers and requires more
research [40]. This is explained when physiological responses
differ from one individual to another, as well as treatment protocols
influence the same heterogeneity of the desired response [41].
However, this limitation is overcome by expanding research in
different sports. This meta-analysis showed that the population
chosen from the different articles is heterogeneous, demonstrating
that the presence of certain SNPs affects the risk of sports injury. This
is consistent with other similar studies [42] where an incidence of
SNPs of the ACTN3 R577X gene associated with a hamstring injury
affecting flexibility, and at the same time, manifesting limitations in
their ranges of joint movement [43], for which the presence of this
polymorphism would give rise to the increase in muscle injuries.
Sports like weightlifting and CrossFit, has the physical
requirements are high [44], for which the presence of an injury is
related to whether the athlete has an ACTN3 R577X polymorphism;
the foregoing reflects that the risk of injury prevails over the
individual who does not manifest it. This is how Miyamoto et al
[45] infer that this polymorphism is responsible for changes in the
sarcomeric cytoskeleton leading to muscle stiffness and prevalence
of injury [46]. One of the limitations found in this study was the
diversity of polymorphisms associated with sports injuries as
well as the limited availability of research on a gene or a defined
polymorphism. For this reason, I2 was very high in contrast to
some studies in other areas for treatment [47], a situation that
differs from the study proposed by Fang et al [48] who found
significant associations for the alleles of the ACTN3 gene with
the different sports disciplines and performance. Regarding the
COL5A1 polymorphism, it was possible to estimate the statistical
significance, allowing to determine that the incidence of lesions
is associated with this gene, which is confirmed in other studies [36], by indicating that type V collagen generates an important
regulation in the diameter of the fibers. as in the assembly process
of the collagen fiber [49], essential for the moments of traction and
compression that are exerted during the start of weightlifting.
This is highlighted by Raleigh (2012) [50], when indicating
about the implications of epigenetic factors in gene regulation
beyond polymorphisms and modification of sports performance.
Therefore, robust replication of studies in large cohorts of athletes
is required before the findings can be applied to practice in sport.
The limitations of the study are reflected in the limited availability
of literature on the subject of sports genomics and its interaction
with sports injuries, which is supported by various investigations
on the subject [51,52]. Although the overall risk of bias within those
included studies were considered low, some reports that were
excluded had biases due to selective reports and incomplete data.
Therefore, it is recommended that future studies include reporting
on all measured allele frequencies rather than focusing only on the
most common genetic variants.
Conclusions
The meta-analysis allowed us to determine that the field of sports genomics is poorly explored in Colombia and that it requires more research to generate genetic profiles related to sports injuries. In general, 2 possible SNPs of the different genes that are related to sports injuries have been identified, which can be used as preliminary evidence to develop an investigation focused on the polygenic nature of complex traits related to specific pathologies of the muscular system and tendinous. For the ACTN3 and COL5A1 genes, a risk and positive association were observed, with statistical significance p >< 0.05, which allows generating new horizons from this knowledge, that help to reveal the pathophysiology of sports injuries. The Authors declare not to present any conflict of interest and their participation in the entire study process.
Ethical-Legal Aspects
This study is cataloged as a risk-free investigation by not carrying out any intervention or intentional modification of the biological, physiological, psychological, or social variables of individuals, as stipulated in resolution 8430 of 1993 [53] and following the guidelines of the declaration Helsinki as PRISMA’s guide to meta-analysis. The present project was approved by the Ethics Committee of the Universidad del Cauca through code 4925 called Sports Injury Prevention.
References
- Wang DG, Fan JB, Siao CJ, Berno A, Young P, et al. (1998) Large-scale identification, mapping, and genotyping of single- nucleotide polymorphisms in the human genome. Science (80-) 280(5366): 1077-1082.
- Aasa U, Svartholm I, Andersson F, Berglund L (2017) Injuries among weightlifters and powerlifters: A systematic review. Br J Sports Med 51(4): 211-219.
- Siewe J, Rudat J, Röllinghoff M, Schlegel UJ, Eysel P, et al. (2011) Injuries and overuse syndromes in powerlifting. Int J Sports Med 32(9): 703-711.
- Zurita Ortega F, Fernández García R, Cachón Zagalaz J, Linares Girela D, Pérez Cortés AJ, et al. (2015) Psychosomatic aspects involved in sports injuries. Cuad Psicol del Deport. 14(2): 81-88.
- Rodas G, Pruna R, Artells R (2009) Clinical Practice Guide for injuries, Epidemiology, diagnosis, treatment and prevention. Apunt Med l’Esport. 164: 179-203.
- Jimenez Diaz F, Goitz H, Bouffard A (2010) Clinical and Ultrasound Diagnosis of Muscle Lesions. Arch Med del Deport. 27(140): 465-476.
- Vaamonde D, Vega lozano A, Canales Dominguez A, Barossi J (2019) Prevention and treatment of sports-related anterior cruciate ligament injuries. Rev Andaluza Med del Deport. 12(4): 381-385.
- Haugen T, Danielsen J, McGhie D, Sandbakk, Ettema G, et al. (2018) Kinematic stride cycle asymmetry is not associated with sprint performance and injury prevalence in athletic sprinters. Scand J Med Sci Sport. 28(3): 1001-1008.
- Widmann M, Nieß AM, Munz B (2019) Physical Exercise and Epigenetic Modifications in Skeletal Muscle. Sport Med. 49(4): 509-523.
- Camera DM, Smiles WJ, Hawley JA (2016) Exercise-induced skeletal muscle signaling pathways and human athletic performance. Free Radic Biol Med. 98: 131-143.
- Yoon J, Bae M, Kang H, Kim T (2018) Descriptive epidemiology of sports injury and illness during the Rio 2016 Olympic Games: A prospective cohort study for Korean team. Int J Sport Sci Coach. 13(6): 939-946.
- Leventera L, Eekb F, Lames M (2018) Intra-seasonal variation of injury patterns among German Bundesliga soccer players. J Sci Med Sport. 5(1): 24-29.
- Jayanthi NA, Labella CR, Fischer D, Pasulka J, Dugas LR, et al. (2015) Sports-specialized intensive training and the risk of injury in young athletes: A clinical case-control study. Am J Sports Med. 43(4): 794-801.
- Larruskain JON, Celorrio D, Barrio I, Odriozola A, Gil SM, et al. (2018) Genetic Variants and Hamstring Injury in Soccer: An Association and Validation Study. Med Sci Sport Exerc. 361-368.
- Pitsiladis YP, Tanaka M, Eynon N, Bouchard C, North KN, et al. (2016) Athlome project consortium: A concerted effort to discover genomic and other “omic” markers of athletic performance. Physiol Genomics. 48(3):183-190.
- Zhang Q, Cao Y, Chen J, Shen J, Ke D, et al. (2019) ACTN3 is associated with children’s physical fitness in Han Chinese. Mol Genet Genomics. 294(1): 47-56.
- Ficek K, Cieszczyk P, Kaczmarczyk M, Maciejewska-Karłowska A, Sawczuk M, et al. (2013) Gene variants within the COL1A1 gene are associated with reduced anterior cruciate ligament injury in professional soccer players. J Sci Med Sport 16(5): 396-400.
- Heffernan SM, Kilduff LP, Erskine RM, Day SH, Stebbings GK, et al. (2017) COL5A1 gene variants previously associated with reduced soft tissue injury risk are associated with elite athlete status in rugby. BMC Genomics 18(Suppl 8).
- Pruna R, Artells R (2015) How the genetic component can affect the injuries of athletes. Apunt Med l’Esport 50(186): 73-78.
- Massidda M, Voisin S, Culigioni C, Piras F, Cugia P, et al. (2019) ACTN3 R577X Polymorphism Is Associated with the Incidence and Severity of Injuries in Professional Football Players. Clin J Sport Med 29(1): 57-61.
- Moreno V, Areces F, Ruiz-Vicente D, Ordovás JM, Del Coso J, et al. (2020) Influence of the ACTN3 R577X genotype on the injury epidemiology of marathon runners. PLoS One 15(1): 1-11.
- Delmonico MJ, Kostek MC, Doldo NA, Hand BD, Walsh S, et al. (2007) Alpha-actinin-3 (ACTN3) R577X polymorphism influences knee extensor peak power response to strength training in older men and women. J Gerontol Med Sci 62(2): 206-212.
- Orysiak J, Busko K, Michalski R, Mazur-Rózycka J, Gajewski J, et al. (2014) Relationship between ACTN3 R577x polymorphism and maximal power output in elite polish athletes. Med 50(5): 303-308.
- Fattahi Z, Najmabadi H (2012) Prevalence of ACTN3 (the athlete gene) R577X polymorphism in Iranian population. Vol. 14, Iranian Red Crescent Medical Journal.
- Birk DE, Fitch JM, Babiarz JP, Doane KJ, Linsenmayer TF (1990) Collagen fibrillogenesis in vitro: Interaction of types I and V collagen regulates fibril diameter. J Cell Sci 95(4): 649-657.
- Collins M, Posthumus M (2011) Type V collagen genotype and exercise-related phenotype relationships: A novel hypothesis. Exerc Sport Sci Rev 39(4): 191-198.
- Urrutia G, Bonfill X (2010) Declaracion PRISMA: una propuesta para mejorar la publicacion de revisiones sistematicas y metaanalisis. Med Clin (Barc) 135(11): 507-511.
- Bassini A, Cameron LC (2014) Sportomics: Building a new concept in metabolic studies and exercise science. Biochem Biophys Res Commun 445(4): 708-716.
- Moher D, Liberati A, Tetzlaff J, Altman DG, Altman D, et al. (2009) Preferred reporting items for systematic reviews and meta-analyses: The PRISMA statement. PLoS Med 6(7): e1000097.
- Sterne JAC, Savović J, Page MJ, Elbers RG, Blencowe NS, et al. (2019) RoB 2: A revised tool for assessing risk of bias in randomised trials. BMJ 366: 1-8.
- Higgins JP, Green S (2014) Manual Cochrane de revisiones sistemáticas de intervenciones, 2011.
- Ruaro MB, Batista CV, Knaut SDAM, Dubiela A, Suckow PPT, Ruaro JA, et al. (2014) Uso da kinesio taping na dor lombar: revisão sistemática. ConScientiae Saúde 13(1).
- Chen C, Sun Y, Liang H, Yu D, Hu S, et al. (2017) A meta-analysis of the association of CKM gene rs8111989 polymorphism with sport performance. Biol Sport 34(4): 323-330.
- Sarzynski MA, Ghosh S, Bouchard C (2017) Genomic and transcriptomic predictors of response levels to endurance exercise training. J Physiol 595(9): 2931-2939.
- Bouchard C (2015) Exercise genomics-A paradigm shift is needed: A commentary. Br J Sports Med 49(23): 1492-1496.
- Pabalan N, Tharabenjasin P, Phababpha S, Jarjanazi H (2018) Association of COL5A1 gene polymorphisms and risk of tendon-ligament injuries among Caucasians: a meta-analysis. 4, Sports Medicine - Open. 2018.
- Hrstka R, Michalova E, Vojtesek B (2013) Impaired pre-mRNA processing and altered architecture of 3’ untranslated regions contribute to the development of human disorders. Int J Mol Sci 14(8): 15681-15694.
- Lulińska-Kuklik E, Rahim M, Domańska-Senderowska D, Ficek K, Michałowska-Sawczyn M, et al. (2018) Interactions between COL5A1 Gene and Risk of the Anterior Cruciate Ligament Rupture. J Hum Kinet 62(1): 65-71.
- Kirk EA, Moore CW, Chater-Diehl EJ, Singh SM, Rice CL, et al. (2016) Human COL5A1 polymorphisms and quadriceps muscle–tendon mechanical stiffness in vivo. Exp Physiol. 101(12): 1581-1592.
- Sližik M, Pospieszna B, Gronek J, Sworek R (2017) Are SNIP’s still desirable in sports genomics? Trends Sport Sci. 24(1): 13-18.
- Sparks LM (2017) Exercise training response heterogeneity: physiological and molecular insights. Diabetologia. 60(12): 2329-2336.
- Wang C, Li H, Chen K, Wu B, Liu H, et al. (2017) Association of polymorphisms rs1800012 in COL1A1 with sports-related tendon and ligament injuries: A meta-analysis. Oncotarget 8(16): 27627-27634.
- Morales-Artacho AJ, Lacourpaille L, Guilhem G (2017) Effects of warm-up on hamstring muscles stiffness: Cycling vs foam rolling. Scand J Med Sci Sport. 27(12): 1959-1969.
- Nyberg M, Fiorenza M, Lund A, Christensen M, RØmer T, et al. (2016) Adaptations to Speed Endurance Training in Highly Trained Soccer Players. 48(7), Medicine and Science in Sports and Exercise. 1355-1364.
- Miyamoto N, Miyamoto-Mikami E, Hirata K, Kimura N, Fuku N, et al. (2018) Association analysis of the ACTN3 R577X polymorphism with passive muscle stiffness and muscle strain injury. Scand J Med Sci Sport 28(3): 1209-1214.
- Bosnyák E, Trájer E, Udvardy A, Komka Z, Protzner A, et al. (2015) ACE and ACTN3 genes polymorphisms among female Hungarian athletes in the aspect of sport disciplines. Acta Physiol Hung 102(4): 451-458.
- Zietzer A, Buschmann EE, Janke D, Li L, Brix M, et al. (2017) Acute physical exercise and long-term individual shear rate therapy increase telomerase activity in human peripheral blood mononuclear cells. Acta Physiol 220(2): 251-262.
- Fang M, Yang Y, Li X, Zhou F, Gao C, et al. (2013) The Association of Sport Performance with ACE and ACTN3 Genetic Polymorphisms: A Systematic Review and Meta-Analysis. PLoS One 8(1): 1-9.
- Saunders CJ, Van Der Merwe L, Cook J, Handley CJ, Collins M, et al. (2015) September A V. Extracellular matrix proteins interact with cell-signaling pathways in modifying risk of achilles tendinopathy. J Orthop Res 33(6): 898-903.
- Raleigh SM (2012) Epigenetic regulation of the ACE gene might be more relevant to endurance physiology than the I/D polymorphism. J Appl Physiol 112(6): 1082-1083.
- Fernandez E, Alvarez M, Podhajcer Os, Stolovitzky G (2015) Functional Genomics: In Search of the Function of Genes. Actas La Acad Nac Ciencias (Cordoba, Argentina).2015; XIII(Junio).
- Wang G, Padmanabhan S, Wolfarth B, Fuku N, Lucia A, et al. (2013) Genomics of elite sporting performance: What little we know and necessary advances. Adv Genet 84: 123-149.
- (1993) Ministry of Health and Social Protection Colombia. Resolución 8430: 1-12.
